A

Absorption, see Dietary copper Acelp,

copper detoxification, 577 gene targets, 482 structure and function, 577

Aceruloplasminemia, clinical features, 25, 190

Actin, see F-actin AD, see Alzheimer's disease Albumin, copper binding, 9,11,

189,344 ALS, see Amyotrophic lateral

sclerosis Alzheimer's disease (AD),

amyloid-~ copper role, 26, 270, 289,311

brain lesion characteristics, 307,308

metal ion homeostasis, 309-311 oxidative metabolism, 311 presenilin gene mutations, 307

am! cluster, Streptomyces, 515 Amicyanin,

crystal structure refinement with molecular dynamics, 95

molecular modeling of protein interactions, 92

Amyloid-~, copper,

Alzheimer's disease ROLE, 270,289,311

589

Index

transport, 270, 289, 297 precursor protein,

antioxidant responses, 309 copper homeostasis role, 309 copper reduction, 309 domains, 308 functions, 308, 309

Amyotrophic lateral sclerosis (ALS),

apoptosis in neurodegeneration, 286-288

copper chelators in therapy, 306,307

copper / zinc superoxide dismutase mutations,

aggregation, 306 copper binding, 284 folding variants, 284, 306 gain-of-function mutants,

304,305 neurodegeneration

mechanisms, 284-288, 306

overview, 270 types, 283

glutamate transporter loss, 304 incidence, 304 sporadic vs familial disease,

282,304 Angiogenesis,

cancer growth dependence, 455,456

590

copper role, 24, 456 tetrathiomolybdate inhibition,

cancer clinical trials, 457 diseases of

neovascularization, 458 preclinical studies, 456, 457

Aquatic organisms, cell signaling effects of copper,

calcium homeostasis, 424-426 tyrosine kinase cascade, 424

cellular mechanisms of copper homeostasis, 418

copper effects on cell compartments,

endoplasmic reticulum, 420,421

lysosomes,422,423 mitochondria, 421,422 plasma membrane,419,420

genotoxicity of copper,423 neurone effects of copper, 426

Arabidopsis thaliana, copper,

content, 543 essentiality, 543, 544 homeostasis networks,

CCH chaperone, 552-554 chelation systems, 545,546 endomembrane

transporters, 550, 552 plasma membrane

transporters, 546, 548-550

oxidative stress induction and defenses, 544, 545

transport and distribution proteins,

chaperone proteins, 488, 489 COPTl, 486, 487

Index

CPx transporters, 488 RANI, 487, 488

iron metabolism, copper role, 491 copper-independent

acquisition, 489 storage, 490

metal tolerance, 543 Ascorbate oxidase, Streptomyces,

517,519 ATOXl, see HAHI/ ATOXI ATP, copper uptake energetics,

195 ATP7 A, see MNK ATP7B, see PINA; WND Atxl,

Arabidopsis homolog, see CCH, Ccc2 interactions, 574 Chlamydomonas reinhardtii, 494 copper chaperone, 253,254,265

Azurin, water-protein interaction analysis, 98

B

Bag-I, Hsp70 interactions, 358 Bag-3, see Bis Bile, copper excretion, 16, 17 Bis,

CAIR-l clone, 365, 366 copper regulation of expression,

359,360 domains, 365 gene cloning, 359 phosphorylation, 365 sequence, 359 subcellular localization and

copper effects, 360, 361 synthesis and regulation in

HeLa cells, 361, 364

Index

tissue distribution, 359 bId mutants, see Streptomyces Blue copper proteins,

cupredoxins,

C

copper binding sites, 54 electron transfer processes,

56,57 spectroscopic characterization,

54 structures,54

overview of family, 54 plastocyanin electron transfer

process, see Plastocyanin sequence homology, 58-60 similarity analysis with respect

to molecular interaction properties,

descriptor classification, 67 molecular interaction field

similarity analysis, 67,68

overview, 61 protein interaction property

similarity analysis, 63, 65-67

sequence and structure analysis, 63

subfamily members and redox properties, 54, 55

CAB45584, Streptomyces, 519 CAB50963, Streptomyces, 519,

520 Caco-2 cell, see Intestine Cadherin, see E-cadherin Calcium, copper effects in aquatic

organism homeostasis, 424-426

591

Calcium ATPase, copper effects in aquatic

organisms, 419, 420, 424 P-type ATPase homology, 264

Cancer, angiogenesis, see Angiogenesis copper metabolism, 24, 25

Cartilage matrix glycoprotein (CMGP), copper binding and function, 21

Ccc2, Atx1 interactions, 574 Chlamydomonas reinhardtii, 494 copper,

loading of Fet3p, 241, 574 transport, 227

CCH, Atx1 homology, 552 C-domainfeatures, 552,553 expression and localization in

Arabidopsis, 553, 554 structure, 552

CCS, copper chaperone, 8, 190,253,

344,574 homology modeling, 92, 93 superoxide dismutase copper

delivery, 574, 575 Ceruloplasmin,

aceruloplasminemia, 25,190 acute phase reaction response,

20,24 apoceruloplasminemia,20 copper center types, 236, 392 copper distribution to tissues,

11,12,14,15,21,484 ferroxidase mechanism, 162, 163 function and diseases, 18,348 iron uptake role, 196, 236, 344

592

structure, 20 Wilson's disease levels, 235

Childhood cirrhosis, see Indian childhood cirrhosis; Non­Indian childhood cirrhosis

Chlamydomonas reinhardtii, copper, assimilation, 492 Crr1 as master regulator, 494 deficiency adaptation,

iron,

cytochrome-c6 role, 491, 492 gene targets, 492 hypoxic expression of

deficiency targets, 493,494

plastocyanin role, 491, 492

assimilation, 494 copper role in metabolism,

496,497 deficiency-induced genes,

494,496 transporters and metabolic

enzymes, 495,496 CMGP, see Cartilage matrix

glycoprotein Confocal microscopy, intestine

tight junction copper toxicity studies,

E-cadherin staining, 409 F-actin localization, 407-411 fixation, 406, 407 image acquisition and analysis,

408 cop operon,

copper regulation, 179 genes, 177

CopA, discovery, 527

Index

metal specificity, 528 purification and properties,

528,530 CopB,

discovery, 527 kinetic parameters, 530, 531 metal specificity, 530 purification and properties, 531

Copper-containing amine oxidase, function and Menkes disease expression profiling, 347

Copper-dependent ceramide hydroxylase, function and Menkes disease expression profiling, 349

Copper-dependent sulfhydryl oxidase, function and Menkes disease expression profiling, 349

Copper deficiency, Chlamydomonas reinhardtii

adaptation, cytochrome-c6 role, 491, 492 gene targets, 492 hypoxic expression of

deficiency targets, 493,494

plastocyanin role, 491, 492 developmental effects, 249 features, 3, 4 genetic diseases, see Menkes

disease; Occipital horn syndrome

pig model, 235 Copper proteins, see also specific

proteins, copper center types and

classification by prosthetic centers, 81,83-85, 153, 154

Index

molecular modeling, see Molecular modeling, copper proteins

types and functions, overview, 81,82

Copper toxicosis, see Toxicity, copper

Copper / zinc superoxide dismutase,

amyotrophic lateral sclerosis mutations,

aggregation, 306 copper binding, 284 folding variants, 284, 306 gain-of-function mutants,

304,305 neurodegeneration

mechanisms, 284-288, 306

overview, 270 types, 283

antioxidant efficiency, 283 copper,

binding and function, 17, 19, 305

detoxification in yeast, 577 homology modeling, 92, 93 molecular dynamics simulation,

crystal structure refinement, 94 mutant studies, 97, 98 spectra analysis, 96, 97

molecular modeling, 91 peroxidase activity, 305, 306 pro-oxidant activity, 284 reactions, 305 redox reactions, 283, 284

COPT1, Arabidopsis thaliana copper transport, 486, 487, 547,549

593

COPT2, Arabidopsis thaliana copper transport, 547, 550

CopY, copper transfer mechanism

from CopZ, 181-184 DNA binding, 179, 180,

531-533 domains, 179 metal-binding studies, 179, 180 purification and properties, 533 structure, 531

CopZ, CopA interactions, 181 copper-induced conformational

change, 537, 538 CopY as copper transfer target,

181-184 intracellular copper routing,

533,535 metal-binding studies, 178,

179,538,539 sequence homology with other

copper chaperones, 178, 538,539

structure, 533,535,537,540 Cox17,

copper chaperone, 190,253, 344,575

Schizosaccharomyces pombe homolog, 580

CPx transporters, Arabidopsis thaliana, 488

Crr1, copper regulation in Chlamydomonas reinhardtii, 494

Ctr proteins, copper uptake,

mammalian cells, 192, 194 regulation, 195, 196

594

yeast, Saccharomyces cerevisiae,

191,252,253,482, 572-575

Schizosaccharomyces pombe, 578-580

energetics of copper uptake, 195, 197

human protein, see hCTRl Mac1p regulation of gene

expression, 476 structures,

Ctrlp, 572, 573 Ctr3p, 572, 573 Ctr4, 578, 579 Ctr5,580

transcriptional regulation by Maclp,476,576,577

Cufl, copper sensing, 581 deletion phenotypes, 580, 581 opposing regulation of copper

and iron genes, 581, 582 Cupredoxins, see Blue copper

proteins; Plastocyanin Cytochrome c oxidase,

bovine heart enzyme, metal content and

crystallization effects, 132, 133

phospholipid content, 133 subunits, 133

copper binding and function, crystal structures of redox­

active metal sites, 140, 141, 143

electron transfer mechanism, 137

overview, 17, 131

oxygen reduction, chemistry, 137, 138 mechanism, 143, 144 resonance Raman

Index

spectroscopy, 138, 140 proton transfer,

Fourier transform infrared spectroscopy studies of redox-coupled conformational change, 147, 149

paths, 144-146 proton pumping

mechanisms, 149, 150 redox-coupled

conforma tional change, 146, 147

redox-coupled transfer mechanisms, 146

transfer through peptide bonds, 147

redox titration experiments, 135, 137

spectral studies, 134, 135 Cox17 copper chaperone, 190,

253,344,575 crystallization, 132 function and Menkes disease

expression profiling, 347 function, 131 purification, 131, 132 Streptomyces, 516, 517

Cytochrome-c6, Chlamydomonas reinhardtii copper deficiency adaptation, 491, 492

D

Deficiency, copper, see Copper deficiency

Index

Diamine oxidase, active site modeling, 93

Dietary copper, absorption, 4-9, 189, 190,250,

254,257,388-390,484 contents in food and tissue, 3,

4,370,385 deficiency effects, 3, 4 preloading effects on copper

homeostasis, 390 Recommended Daily Allowance,

3,385 WIlson disease management, 454

Differential display, copper status effects on gene

expression, 352, 353 Menkes disease expression

profiling, fibroblasts, 352 preliminary results, 351

overview, 349, 351 DMTI/Nramp2,

copper, transport, 7 uptake in yeast, 192

function and diseases, 18 metal specificity, 7, 13

Dopamine j3-hydroxylase, function

E

and Menkes disease expression profiling, 345, 346

E-cadherin, intestine tight junction copper toxicity studies, 409

EIN2, Arabidopsis copper transport, 547, 548

Electron paramagnetic resonance (EPR), Fet3, 155, 157

595

Electron spin-echo envelope modulation (ESEEM),

Fet3 copper-binding site structure, 157-160

principles, 157 Embryogenesis, copper role, 22 Endoplasmic reticulum (ER),

copper effects in aquatic organisms, 420, 421

plant copper transporters, 550, 552

Enterococcus hirae, advantages in copper studies,

527 copper ATPases, see CopA;

CopB copper proteins, see cop

operon; CopY; CopZ EPR, see Electron paramagnetic

resonance ER, see Endoplasmic reticulum ESEEM, see Electron spin-echo

envelope modulation EXAFS, see Extended X-ray

absorption fine structure Excretion, copper, 5, 16, 17, 250,

254,257,386 Extended X-ray absorption fine

structure (EXAFS),

F

CopZ, 178, 179 Fet3 binuclear type-3 copper­

binding site structure, 160-162

F-actin, intestine tight junction copper toxicity studies, 407-411

Factor V,

596

function and Menkes disease expression profiling, 348,349

homology modeling, 92 Factor VIII, function and Menkes

disease expression profiling, 348,349

Ferroxidases, see Ceruloplasmin; Fet3p; Hephaestin

Fet3p, copper center types, 153-156 copper loading,

assay, 243 Ccc2 role, 241 chloride role, 243, 244 vacuolar gene roles, 242, 243

crystallization, 169 electron spin-echo envelope

modulation, copper­binding site structure studies, 157-160

extended X-ray absorption fine structure, binuclear type-3 copper-binding site structure, 160-162

ferroxidase activity, assays, 169, 170,239 kinetic constants, 168, 169,

172,239 mechanism, 163-165, 167, 168 prospects for study, 172, 173 reduction potential and

substrate specificity, 171,172

stopped-flow, 169, 170 Ftr1p complex, 240, 241, 482, 483 homology modeling,

copper-binding sites, 156, 157 molecular modeling, 92

Index

identification, 238 iron transport model, 237, 238 iron uptake, 482, 483 mutagenesis studies of iron

transport, 239, 240 oxygen consumption, 238, 239 recombinant protein expression

systems, insect cells, 167, 168 yeast, 168, 169

trafficking, 241 Fet4, metal specificity, 241 Force field, molecular dynamics

simulation, 90, 91 Fourier transform infrared

spectroscopy (FTIR), studies of redox-coupled conformational change in cytochrome c oxidase, 147, 149

Fox1, Chlamydomonas reinhardtii, 494

Fre proteins, copper reduction prior to yeast

uptake, 195 iron regulation of expression, 196 transcriptional regulation by

Mac1p, 576, 577 FTIR, see Fourier transform

infrared spectroscopy Ftr1p, Fet3p complex, 240, 241,

482,483 Fulminant hepatitis, see Long­

Evans Cinnamon rat,

G

Gestation, copper metabolism, 23 Glutathione,

copper chaperone, 8, 9,190, 279,418

Index

H

intestinal epithelial copper handling, 389

liver copper handling, 391

HAH1/ ATOX1, copper chaperone, 7, 8, 190,

254,265,266 function and diseases, 18 knockout mouse phenotype, 9

hCTR1, chaperones for copper delivery, 8 copper transport, 6, 7,231,

232,254 domains, 253 function and diseases, 18 release of copper, 15 structure, 6

Heat shock proteins (HSPs), classes, 358 regulation of expression, 358

Hephaestin, function and diseases, 18,21,348

Histidine, copper binding in proteins, 9 copper transport, 9,12

HSPs, see Heat shock proteins

I

ICC, see Indian childhood cirrhosis Indian childhood cirrhosis (ICC),

animal models, 260, 261 causes, 260 geographic distribution, 370 heredity, 260

Infection, copper metabolism, 24 Inflammation, copper

metabolism, 24 Intestine,

597

chronic copper toxicity effects, 388-390

copper absorption, 4-9, 189, 190,250,254,257, 388-390,484

tight junction copper toxicity, Caco-2 cell model,

culture, 398 differentiation and

establishment of tight junctions, 401, 402

overview, 397, 398 clinical significance, 413, 414 copper complexes and

treatment, 402, 403 fluorescence labeling of

proteins and confocal microscopy,

Iron,

E-cadherin staining, 409 F-actin localization, 407-411 fixation, 406, 407 image acquisition and

analysis, 408 oxidative stress role, 411, 413 permeability to extracellular

markers, 400, 401 protein kinase C role, 413 reversibility of toxicity,

404,406 transepithelial electrical

resistance, 399, 400, 403, 404,406

transmission electron microscopy of ultrastructural changes, 411

absorption, 485 Alzheimer's disease role, 310, 311

598

anemia and copper protein defects, 571

Arabidopsis thaliana metabolism, copper role, 491 copper-independent

acquisition, 489 storage, 490

ceruloplasmin role in uptake, 196,236

Chlamydomonas reinhardtii metabolism,

assimilation, 494 copper role in metabolism,

496,497 deficiency-induced genes,

494,496 transporters and metabolic

enzymes, 495, 496 copper role in mammal

metabolism, 485, 486 distribution, storage, and

regulation in mammals, 485 Parkinson's disease role, 299,

300 yeast metabolism,

copper role in uptake, 196, 240,241,483

distribution, storage, and regulation, 482

Saccharomyces cerevisiae, 236, 237,482,483

Schizosaccharomyces pombe metabolism,

Cufl opposing regulation of copper and iron genes, 581, 582

uptake, 578 IRT1, Arabidopsis copper

transport, 547, 548

Index

L

Laccase, Streptomyces, 517, 519 Lactation, copper metabolism,

23,24 LEC rat, see Long-Evans

Cinnamon rat Lipid peroxidation, copper effects

on cell compartments in aquatic organisms, 419

Liver, chronic copper toxicity effects,

390-392 copper metabolism,

excretion, 16, 17, 257 uptake and transport, 13, 14,

257,391,392 Long-Evans Cinnamon (LEC) rat,

fulminant hepatitis and copper-metallothionein polymers,

Kupffer cell accumulation, 468,469

liver disease onset, 461, 462 penicillamine prevention,

461-463,469,470 subcellular sites of

hepatotoxicity, 465-468 ultrastructure analysis,

462,463 Wilson disease model, 228,

229,260,261,461 LOX, see Lysyl oxidase Lysosome,

copper detoxification, 465-468 copper effects in aquatic

organisms, 422, 423 Lysyloxidase (LOX),

copper binding and function, 21,346,347

Index

Menkes disease expression profiling, 346, 347, 352

M

Mac1p, copper detoxification, 476 CTR transcription regulation,

476,576,577 gene targets, 482 phosphorylation, 478 sensing of copper, 476, 477 thermodynamic model of

copper uptake vs detoxification, 477, 478

a2-Macroglobulin, copper binding, 11

Manganese, Parkinson's disease role, 299, 300

Marine organisms, see Aquatic organisms

Melatonin, circadian rhythm, 201, 203 PINA regulation, 205 regulation, 201, 202, 205, 206 synthesis, 201

Menkes disease, clinical features, 25, 35, 257,

258,323,324 copper protein functions and

expression profiling, ceruplasmin,348 copper-containing amine

oxidase, 347 copper-dependent ceramide

hydroxylase, 349 copper-dependent sulfhydryl

oxidase, 349 cytochrome-c oxidase, 347 differential display,

599

copper status effects on gene expression, 352,353

fibroblasts, 352 overview, 349, 351

dopamine b-hydroxylase, 345,346

factor V, 348, 349 factor VIII, 348, 349 hephaestin, 348 lysyl oxidase, 346, 347, 352 peptidyl a-amidating

monooxygenase,346 prospects for study, 353 superoxide dismutase, 347,

348 tyrosinase, 349

copper transport defects, 209, 240,251

diagnosis, 191,258,328 gene defect, see MNK incidence, 209 intracellular copper transport,

345 laboratory findings, 325, 326 mild disease, 257, 319, 325 molecular basis for variable

clinical phenotypes, 268, 269 mouse models, 259, 260, 281 neurological abnormalities, 281 pathophysiology, 322, 323 treatment, 258, 259, 328-330

MEP, see Molecular electrostatic potential

Metallothioneins, copper-metallothionein

complex, abundance in Wilson disease,

434,435

600

bUndUng, 5, 8, 19,20, 190,418 copper removal by

tetrathiomolybdate, see Tetrathiomolybdate

detoxification Un yeast, 577 Long-Evans Cinnamon rat,

hihnWnanthepatitis,and copper-metallothioneUn polymers,

Kupffer cell accumulation, 468,469

liver disease onset, 461, 462 penicillamUne prevention,

461--463,469,470 subcellular sites of

hepatotoxicity, 465--468

ultrastructure analysis, 462,463

preparation of complexes, 437

pro-oxidant activity, 434 functions, 19, 20, 358 Untestinal epithelial copper

handlUng, 389 liver copper handlUng, 391 metal-responsive elements in

expression regulation, 358 molecular modeling of bUndUng

sites, 93 plants, 545, 546 types, 190,484

Methane monooxygenase, see Particulate methane monooxygenase; Soluble methane monooxygenase

Methanotrophs, applications, 559 methane oxidation pathway, 560

particulate methane monooxygenase, see Particulate methane monooxygenase

soluble methane monooxygenase, see Soluble methane monooxygenase

types and genera, 559

Index

MIF, see Molecular Unteraction field Mitochondria, copper effects Un

aquatic organisms, 421, 422 MNK,

copper, bUndUng sites, 265 transport, 7, 8, 189 uptake regulation, 254, 257

developmental expression, 22 function and diseases, 18 gene,

alternative promoter evidence and characterization, 337-339

clonUng,211 locus, 319 promoter characterization,

336,337 regulation of expression, 336 structure, 209, 210, 261, 319

genotype-phenotype correlation, 321,322

gestation role, 23 lactation role, 24 molecular basis for variable

clinical phenotypes, 268, 269 mottled mouse mutants, 268,

269,319 mutations Un Menkes disease,

25,280,320,321

Index

P-type ATPase family, calcium ATPase homology,

264 cation recognition, 39 copper transport characteris­

tics, 38, 39 homology with other

members, 36, 37, 262, 263 physiological roles, 37, 38 structural differences be­

tween P1- and P2-ATPases, 39, 40

release of copper, 15, 16 splice variants,

ATP7A2-16, 334, 335 detection, 334 NML45, 335, 336 overview, 261, 262, 268,

333,334 structure, 37, 38, 262-266 tissue distribution, 15, 190,262,

364 trafficking,

CD8 reporter fusions, 214 copper-induced trafficking,

267,268 deletion mutant studies,

211-213 intracellular localization, 211 plasma membrane internaliza­

tion signal identification, 218-220,222,223

steps, 223, 225 trans-Golgi network retention

signal identification, 214, 216, 267, 268

Molecular electrostatic potential (MEP), plastocyanin analysis, 76,78

601

Molecular interaction field (MIF), cupredoxin similarity analysis, 67, 68

Molecular modeling, copper

N

proteins, active site building, 93 availability, 99 building and modifying

structures, 86 comparative protein modeling,

building of model, 87, 88 overview, 86, 87 preliminary procedure, 87 refinement and model

quality, 88 computational chemistry, 86 definition, 85 dynamics simulation,

applications, crystal structure refinement,

94,95 interpretation of spectra,

95-98 protein-water interaction

analysis, 98 force field, 90, 91 overview, 88, 89 physics, 89, 90 potential function, 89

homology modeling, 92, 93 molecular graphics, 86 molecular mechanics, 86 mutant studies, 91, 92

Neurone, copper effects in aquatic organisms, 426

NICC, see Non-Indian childhood cirrhosis

602

Nitric oxide (NO), apoptosis role in amyotrophic

lateral sclerosis neurodegeneration, 286-288

reactive nitrogen speces, 279 Nitrous oxide reductase, crystal

structure refinement with molecular dynamics, 94, 95

NML45, structure and function, 335,336

NO, see Nitric oxide Non-Indian childhood cirrhosis

(NICC), animal models, 378, 379 gene,

ATP7B exclusion as candidate gene, 375

complicating factors in mapping, 377, 378

genomic screening, 376, 377 identification, 369, 371, 372 identity by descent and gene

mapping, 372, 374 German population features,

370,371 pathogenesis, 371, 372 prospects for study, 379, 380 Tyrol, Austria population

features, 369-371 Nramp,

o

Arabidopsis copper transport, 547,548

Nramp2, see DMT1/Nramp2

Occipital hom syndrome (OHS), clinical features, 325 diagnosis, 328 epidemiology, 257

Index

gene mutations, 268, 320, 321 genotype-phenotype correlation,

321,322 laboratory findings, 326, 327 mouse models, 259, 260 pathophysiology, 322, 323 treatment, 330

OHS, see Occipital hom syndrome

p

PAM, see Peptidyl a-amidating monooxygenase

Parkinson's disease (PD), clinical features, 289, 290 copper in pathogenesis, 290,

299,300 familial disease, 298 Lewy bodies, 298, 300 oxidative stress role, 299 parkin deletions, 299 selegiline management, 300 susceptibility locus, 299 a-synuclein mutations, 298,

300 transition metals in pathogenesis,

299,300 Particulate methane

monooxygenase (pMMO), copper regulation of expression,

566,567 genes, 564,565 metal binding, 564 prospects for study, 567 species distribution, 564 structure, 565 substrate specificity, 564 subunits, 564

PD, see Parkinson's disease Penicillamine,

Index

hepatotoxicity prevention in Long-Evans Cinnamon rat 461-463,469,470

Wilson disease management, 449,451

Peptidyl a-amidating monooxygenase (PAM), function and Menkes disease expression profiling, 346

Phytochelatin, plant synthases, 546 PINA,

circadian rhythm, 203 copper binding, 204, 206 melatonin synthesis role, 205 structure, 203,204 tissue distribution, 203 Wilson's disease studies, 206,

207 PIPSA, see Protein interaction

property similarity analysis PKC, see Protein kinase C Plant copper homeostasis, see

Arabidopsis thaliana Plasma membrane,

copper effects in aquatic organisms,419,420

plant copper transporters, 546, 548-550

Plastocyanin, see also Blue copper proteins,

Chlamydomonas reinhardtii copper deficiency adapta­tion, 491, 492

electron transfer process, quantitative analysis of thermodynamic and kinetic properties,

advantages over qualitative approaches, 79

603

cytochrome-f interactions, 69 mutant studies, 70 QSAR analysis of structural

determinants of cytochrome-f association,

descriptors, 76 molecular electrostatic

potential analysis, 76,78

overview, 75, 76 QSPR analysis,

descriptors, 71, 72 models, 72, 74, 75 overview, 71

function, 68, 69 molecular dynamics simulation,

crystal structure refinement, 94,95

water-protein interaction analysis, 98

molecular modeling, 91, 92 structure, 69, 70

pMMO, see Particulate methane monooxygenase

Prion protein (PrP), amyloidosis, 302 copper binding and function,

affinity, 105, 118 binding site, 290, 291, 302 carrier models, 109, 110, 120 copper transport, 303, 304 effects on biochemical prop-

erties and structure, 105, 106,303

overview, 21, 22, 25, 26, 270 peptide binding studies, 118,

119,302 prion disease roles, 109, 111,

123,124,126,302,303

604

protein endocytosis induction by copper, 107-110

regulation of copper release at synapse, 108

copper levels in prion disease brain, 126

disease types, 103, 104, 115, 270,301

doppel homology, 116, 117 function of normal protein,

overview, 104, 291, 301, 302 oxidative stress protection,

108,109,111,120,121,123 superoxide dismutase

activity, 106, 121, 123, 291,303

synaptic activity, 117, 118 infectivity, 115, 123, 124 knockout mice, 116-119 pathogenic form conversion,

103,123,290,301 structure, 104, 116 tissue distribution, 117 transmembrane forms, 301

Protein interaction property similarity analysis (PIPSA), cupredoxins, 63, 65-67

Protein kinase C (PKC), intestine tight junction copper toxicity role, 413

PrP, see Prion protein P-type ATPases, see also MNK;

WND, calcium ATPase homology, 264 cation recognition, 39 copper transport characteristics,

38,39 homology wth other members,

36,37,262,263

Q

Index

physiological roles, 37, 38 Streptomyces, 520-522 structural differences between

Pl- and P2-ATPases, 39,40

QSAR, see Quantitative structure­activity relationships

QSPR, see Plastocyanin Quantitative structure-activity

relationships (QSAR), peptides and proteins, 53 plastocyanin analysis of struc­

tural determinants of

R

cytochrome-f association, descriptors, 76 molecular electrostatic

potential analysis, 76, 78 overview, 75, 76

ram cluster, Streptomyces, 511-513 RANI, Arabidopsis thaliana

copper transport, 487, 488, 550,552

RDA, see Recommended Daily Allowance

Reactive oxygen species (ROS), antioxidant defenses, 278 copper oxidation, 417, 418 copper role in generation, 81,

277,278,419 intestine tight junction copper

toxicity role, 411, 413 Parkinson's disease role, 290 plant cellular damage, 544

Recommended Daily Allowance (RDA), copper, 3, 385

Index

Resonance Raman spectroscopy, cytochrome c oxidase oxygen reduction mechanisms, 138,140

ROS, see Reactive oxygen species Rusticyanin, active site modeling,

93

s Saccharomyces cerevisiae,

copper, acquisition,

chaperones,574,575 high-affinity transport,

572-574 low-affinity uptake, 575, 576 transcriptional regulation of

transporters, 576, 577 detoxification, 577 proteins, see specific proteins

iron uptake, copper role, 196,240,241,483 overview, 236, 237, 482, 483

Schizosaccharomyces pombe, advantages in genetic analysis,

577,578 copper transporters, 578-580 Cufl,

copper sensing, 581 deletion phenotypes, 580, 581 opposing regulation of

copper and iron genes, 581,582

iron uptake, 578 Selegiline, Parkinson's disease

management,300 Smf proteins, copper uptake in

yeast, 575, 576 sMMO, see Soluble methane

605

monooxygenase SOD, see Superoxide dismutase Soluble methane monooxygenase

(sMMO), components and subunits,

560,561 copper regulation of expression,

565,566 genes, 561, 562 prospects for study, 567 recombinant protein expression

and copper effects, 563,564

sequence conservation between species, 562

species distribution, 560 structure, 561 substrate specificity, 560

Streptomyces, copper effects on differentiation,

aerial hyphae induction, 508,509

am! cluster role, 515 ram cluster role, 511-513 reproductive growth, 508, 509 strain differences, 510, 511

developmental mutants, bId mutants, 505, 506, 509, 510 whi mutants, 506, 507

genome analysis of copper proteins,

ascorbate oxidase, 517, 519 CAB45584,519 CAB50963,519,520 cytochrome-c oxidase, 516, 517 laccase, 517, 519 overview, 515, 516 P-type ATPases, 520-522 tyrosinase, 519

606

life cycle, 503, 505 signaling in development,

507,508 Superoxide dismutase (SOD), see

also Copper/zinc superoxide dismutase,

function and Menkes disease expression profiling, 347,348

prion protein activity, 106, 121, 123,291,303

types, 347, 348 a-Synuclein, Parkinson's disease

mutations, 298, 300

T

TEER, see Transepithelial electrical resistance

TEM, see Transmission electron microscopy

Tetrathiomolybdate (TTM), angiogenesis inhibition,

cancer clinical trials, 457 diseases of

neovascularization, 458 preclinical studies, 456, 457

clinical applications, 433, 436, 443 copper-metallothionein copper

removal, analysis, 437 selectivity, 439, 440 tetrathiomolybdate-complex

types, 437-439 mouse studies,

intraperitoneal injection, 439 intravenous injection, 439 selectivity of copper

removal, 439, 440 side effects, 440

Index

preparation, 436,437 Wilson disease management,

449,453 Toxicity, copper,

acceptable range of oral intake, 386

acute toxicity, 387, 388 aquatic organisms, see Aquatic

organisms chronic toxicity,

copper intake thresholds, 392,393

intestine, 388-390 liver, 390-392 defenses, 26 genetic diseases, see Indian

childhood cirrhosis; Non-Indian childhood cirrhosis; Wilson disease

idiopathic copper toxicosis, 370,379,380

intake sources, 370 intestinal tight junction toxicity,

Caco-2 cell model, culture, 398 differentiation and

establishment of tight junctions, 401, 402

overview, 397, 398 clinical significance, 413, 414

copper complexes and treatment, 402, 403

fluorescence labeling of proteins and confocal microscopy,

E-cadherin staining, 409 F-actin localization,

407-411 fixation, 406, 407

Index

image acquisition and analysis, 408

oxidative stress role, 411, 413 permeability to extracellular

markers, 400, 401 protein kinase C role, 413 reversibility of toxicity,

404,406 transepithelial electrical

resistance, 399, 400, 403, 404,406

transmission electron microscopy of ultrastructural changes, 411

mechanisms, 357, 370 neurotoxicity, 124 oxidative stress, 81 plants, 544, 545 species susceptibility, 26 yeast detoxification, 577

Transcuprein, copper binding, 9, 11 Transepithelial electrical resistance

(TEER), intestine tight junction copper toxicity, 399, 400,403,404,406

Transmission electron microscopy (TEM), intestine tight junction copper toxicity studies, 411

Trientine, Wilson disease management 448,449,451,453

TTM, see Tetrathiomolybdate Tyrosinase,

function and Menkes disease expression profiling, 349

Streptomyces, 519 Tyrosine kinase, copper effects in

aquatic organisms, 424

607

w whi mutants, see Streptomyces Wilson disease,

animal models, 260, 261 clinical features, 25, 206, 228,

260,269,282,444 copper in pathogenesis, 206,

250,260 diagnosis, 282, 444, 446, 448 frequency, 228, 443 gene defect, see WND liver biopsy, 448 Long-Evans Cinnamon rat

model, 228, 229, 260, 261, 461 molecular basis for variable

clinical phenotypes, 269 neurological degeneration, 282 prognosis,

compliance, 454, 455 recovery, 454 risk factors, 455

screening, 446, 448 treatment,

diet, 454 initial therapy, 452, 453 maintenance therapy, 451, 452 overview, 260, 282, 436 pediatric therapy, 453 penicillamine, 449, 451 pregnancy, 453 presymptomatic therapy, 453 tetrathiomolybdate therapy,

see Tetrathiomolybdate trientine, 448, 449, 451, 453 water treatment, 454 zinc, 448,451,453

WND, ATP-binding domain,

608

nucleotide-binding properties, 41-43

recombinant domain studies, ATP binding, 48, 49 purification, 48

copper transport, 7, 8, 189, 231-233,434,435

developmental expression, 22 domains, 230 function and diseases, 18,231,

434,435,484 gene structure, 229, 262 gestation role, 23 lactation role, 24 MNK homology, 229 mutations in WIlson disease, 444 N-terminal domain,

copper-binding properties, 40,41

copper-dependent domain­domain interactions and regulatory role, 4, 3-45

recombinant domain studies, copper loading and binding,

45,46 expression, 45 histidine tagging and

purification, 46-48 P-type ATPase family,

calcium ATPase homology, 264 cation recognition, 39 copper transport

characteristics, 38, 39 homology wth other

members, 36,37,262, 263 physiological roles, 37, 38 structural differences

between P1- and P2-ATPases, 39, 40

X

Index

PINA splice variant, see PINA release of copper, 16 splice variants, 262, 269 structure, 37, 38, 262-266 subcellular distribution, 190, 191 tissue distribution, 190,262,

365 trafficking,

copper-induced trafficking, 267 intracellular localization,

230,231 steps, 266, 267 trans-Golgi network retention,

266,267

X-ray crystallography, cytochrome c oxidase,

crystallization, 132

z

crystal structures of redox­active metal sites, 140, 141,143

metal content, crystallization effects, 132, 133

Fet3 crystallization, 169 multicopper oxidase structures,

156,157 structure refinement with

molecular dynamics simulation, 94, 95

Zinc, Alzheimer's disease role, 310, 311 Parkinson's disease role, 299, 300 Wilson disease management,

448,451,453 ZIP, Arabidopsis copper transport,

547,548