8
COLOR PLATES Unknown relation to biosynthetic pathway Regulators Streptidine 6-P synthesis Resistance Transporters Phosphatases SPC condensation, last steps dTDP-dihydro- streptosesynthesis NDP- kasugamine biosynthesis NDP-NMLG- biosynthesis strW [stsA B C D E F G] str X V V X U Q P H G F B1 A K S T R D E L M N N T A B C D X E Y F G H I J N O B2 W stsG stsFstsE stsD stsC stsB stsA strO N B2 M L E D R A B1 insA kasT aphD strK strB spcR orf4 STR S.griseus STR S.glaucescens SPC KAS F G H I K S T Z U J K L M N O P Q R A B C D G F E I kac 338 Figure 2.2. Biosynthetic gene clusters for STR-related AGAs. Functionally related groups of genes are differentiated by the color code given below. NMLG, N -methyl-L-glucosamine. Related groups of genes are differentiated by the color code given above.

Aminoglycoside Antibiotics - Color Plates

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  • COLOR PLATES

    Unkn

    own

    rela

    tion

    tobi

    osyn

    thet

    ic pa

    thwa

    yR

    egul

    ator

    s

    Stre

    ptid

    ine

    6-P

    synt

    hesis

    Res

    ista

    nce

    Tran

    spor

    ters

    Phos

    phat

    ases

    SPC

    cond

    ensa

    tion,

    last

    step

    s

    dTDP

    -dih

    ydro

    -st

    rept

    oses

    ynth

    esis

    ND

    P-ka

    suga

    min

    ebi

    osyn

    thes

    isNDP-

    NM

    LG-

    bios

    ynth

    esis

    strW

    [stsA

    B C

    D E

    F G

    ]

    str X

    V VX

    UQ

    PH

    GF

    B1A

    KS

    TR

    DE

    LM

    N

    NT

    AB

    CD

    XE

    YF

    GH

    IJ

    N

    OB2

    Wst

    sGst

    sFst

    sEst

    sDst

    sCst

    sBst

    sAst

    rON

    B2M

    LE

    DR

    AB1

    insA ka

    sT

    aph

    Dst

    rKs

    trB

    spcR

    orf4

    STR

    S.gr

    iseus

    STR

    S.gl

    auce

    scen

    s

    SPC

    KA

    S

    FG

    HI

    KS

    TZ

    UJ

    KL

    MN

    OP

    QR

    AB

    CD

    GF

    EI

    kac 3

    38

    Figu

    re2.

    2.B

    iosy

    nthe

    ticge

    necl

    uste

    rsfo

    rSTR

    -rel

    ated

    AG

    As.

    Fun

    ctio

    nally

    rela

    ted

    gro

    ups

    ofg

    enes

    are

    diffe

    ren

    tiate

    dby

    the

    colo

    rco

    degi

    ven

    belo

    w.N

    MLG

    ,N-m

    ethy

    l-L-g

    luco

    sam

    ine.

    Rel

    ated

    grou

    pso

    fgen

    esar

    edi

    ffere

    ntia

    ted

    byth

    eco

    lorc

    ode

    give

    nab

    ove.

  • COLOR PLATES

    aph

    aph

    parE

    SC

    MT

    UQ

    NP

    XF

    DL

    BA

    ZI

    pph

    YG

    H

    SC

    MT

    UQ

    NP

    FD

    LB

    ZI

    HG

    ribG

    neo

    G

    RIB

    NEO

    PAR

    LIV

    BTR

    H H

    IE

    SC

    UM

    IE

    SC

    MT

    UQ

    NP

    XF

    DL

    BA

    aa

    cC8

    QT

    NP

    XF

    DL

    BA

    Ra

    acC

    8(Y

    )

    livE

    R2T

    SN

    ML

    AB

    CD

    EF

    GH

    IJ

    KO

    PQ

    btrU

    Unkn

    own

    rela

    tion

    tobi

    osyn

    thet

    ic pa

    thwa

    y

    Reg

    ulat

    ors

    Cycli

    tol m

    onom

    erbi

    osyn

    thes

    is

    4-G

    luco

    sam

    inylt

    rans

    fer

    an

    d 3'

    ,4'-m

    odific

    atio

    n(4

    galac

    tosylt

    ransfe

    r inH

    yg)

    Res

    ista

    nce

    Tran

    spor

    ters

    Rib

    osta

    myc

    in3

    -gl

    ucos

    amin

    yl tra

    nsfe

    ra

    nd

    mod

    ificat

    ion

    (NM-

    family

    )

    Phos

    phat

    ases

    6'-m

    odific

    atio

    n(bi

    functi

    onali

    n NM-

    fam

    ily, a

    lso fo

    r 6

    mo

    dific

    atio

    n)

    2DO

    S 5-

    ribos

    yltra

    nsfe

    ra

    nd

    mod

    ificat

    ion

    (NM-

    fam

    ily)

    gene

    s out

    side

    of t

    he cl

    uste

    rs

    Sens

    or/k

    inas

    ere

    gula

    tor s

    yste

    m

    A B

    AX

    OV

    WY

    Figu

    re2.

    9.B

    iosy

    nthe

    ticge

    necl

    uste

    rsfo

    rNEO

    -fam

    ilyA

    GA

    s.Fu

    nct

    iona

    llyre

    late

    dgr

    ou

    pso

    fgen

    esar

    edi

    ffere

    ntia

    ted

    byth

    eco

    lorc

    ode

    give

    nbe

    low

    :(A)

    colo

    rco

    deu

    sed

    inal

    lgen

    etic

    map

    sfo

    r2D

    OS

    and

    2DO

    S-re

    late

    dA

    GA

    s;(B

    )co

    lorc

    ode

    forp

    athw

    ay-s

    peci

    ficfu

    nctio

    nsin

    the

    NEO

    fam

    ily.

  • COLOR PLATES

    kanZ

    tobE

    genN D T I H G F A Y E V U X B2 K B3 B4P W S2 D1 M2 D2 C S1 M1 D3 Q OB1

    T B Q Z S1 C D2 M2 M1 L U A D3 O RD1 S2 (Tn)

    Y X W A G H I R E T B Q S1 S2C D J K L O P UD3kmrD2 M2 M1

    GEN

    KAN

    TOB

    gmrA gmrB

    Figure 2.15. Biosynthetic gene clusters for KAN/GEN-related AGAs. 2DOS 6-glycosyltransfer and modification-specific genes, all other colors see Figure 2.9.

    "erosion zone"

    1 2

    FOR M. olivasterosp ora

    IST

    FOR? Frankia CcI3

    forY H I J Q W V M S E O L2 D P B K Z X G N A L R O F E D C fmrP B Afmr fosG

    3357 3358 3359 3360 3361 3362 3363 33643365

    33663367

    3368 3369 3370 3371 3372 3373 3374 3375

    imrA istA D P B J F G1 Z H W Q C L3 L I S N X M L2 O E

    Figure 2.22. Biosynthetic gene clusters for fortimicin (FOR), the putative FOR clusterfrom Frankia sp. CcI3 (fra cluster, cf. Table 18) and istamycin (IST) AGAs. Latecyclitol modification, for all other colors see Figure 2.9. See color plates.

    APR Streptoall.hindustanus

    APR S.tenebrarius

    HYG

    aprR2

    aprN

    hygV W A K U D O E P X L J Y N C M S T I H G

    W V U A kamB O D1 F G H I J K C S E P D2 D3 Q D4 Z L D5

    R1 N W V B aprA kamB aprO D1 F G H I J K M

    M

    F

    C S E P D2 D3 Q D4 Z L D5CU tatA

    Figure 2.25. Biosynthetic gene clusters for APR and HYG-B. octose synthase, transfer,

    modification (APR), 8Glycosyltransfer/modification (APR), HYG-specific genes; allother colors see Figure 2.9.

  • COLOR PLATES

    Helix 44

    (a)

    (b)530 Loop

    Figure 5.2. Design of a model oligonucleotide for the decoding site. See text for fullcaption.

    (a)

    (b)

    Figure 5.3. NMR structure of the A-site oligonucleotide. See text for full caption.

  • COLOR PLATES

    (a) (b)

    Figure 5.5. NMR structures of paromomycin and gentamicin C1a in complex with theA-site oligonucleotide. See text for full caption.

    (a) (b)

    Figure 5.7. Structural origins of aminoglycoside specificity. See text for full caption.

  • COLOR PLATES

    Figure 6.3. Conserved interactions between the prokaryotic A-site and the neaminecore of 4,5- and 4,6-disubstituted aminoglycosides as deduced from crystalstructures.1,3,6,10,12 20

    (a)

    (c)

    (b)

    (d)

    Figure 6.5. The observed structures of the resting off state of the prokaryotic (a(references24), b (reference25), c (reference6), d (reference25), e (reference9), f (reference3),and the eukaryotic (g (reference5), h (reference26)) cytoplasmic A-site.

  • COLOR PLATES

    (e)

    (g)

    (f)

    (h)

    Figure 6.5. (continued )

    Figure 10.1. Schematic illustration of the life cycle of HIV-1. See text for full caption.

  • COLOR PLATES

    Figure 10.3. Schematic view of the HIV-1 genome, showing gene structure and splicingpatterns, as well as important RNA sites localized in the 5-long terminal repeat (LTR)and the -site.

    Figure 10.8. Left : The sequence of RRE IIB, a fragment used to study RREligandbinding. Right : The components of our solid-phase assay that utilize the native RREsequence.

    Major Groove

    Minor Groove

    Figure 11.2. Globular conformations of an A-type duplex (left) and a B-type duplex(right), generally seen for RNARNA and DNADNA duplexes, respectively. See text forfull caption.