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Experimental Methods Class Notes June 6, 2001
Class Notes: June 6
Mutations and SNPs:
we use SNPs for Mappin
!enot"pin: to identif" indi#idual enomes
P$%0s are a famil" of en&"mes in the li#erthat modif" drus
and determine whether a
dru will wor' in the human meta(olism or
not)
*ou +an impro#e the odds of dru su++ess
(" +omparin results to people with the+orre+t- SNP at the p$%0
of +hoi+e)
S+reenin is +arried out ("
+on#entional methods
S+annin lare populations is done
(" mi+roarra"s, PC., or se/uen+in)
Microarray screening of SNPs
Why cant you unboil an egg?
Can proteins repli+ateNo, (ut the" +an +ause other proteins to
unfold)
1
!enomi+ N
PC. frament: reion of
interest
PC.
S"stemati+all" +hane ea+h
olio (" one (ase pair)
106possiblecompounds
1000 possiblecompounds
100 possiblecompounds
Today thebottleneckis here, and itsCaused bymetabolism
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8/13/2019 Mutations and SNPs
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Experimental Methods Class Notes June 6, 2001
Stanle" Pruissner is a s+ientist who dis+o#ered prions, the
unfolded proteins that
sometimes +ause disease li'e Mad Cow)
a#id Eisen(ur is a 3C4 professor who wants to ma'e a data(ase of
fun+tionall"5
related proteins)
Protein Folding
Su+l"+in is a protease +ommonl" found in deterents and +onta+t
lens solutions)
Chaperones
e)) eat Sho+' Proteins 7SP8 that a++elerate protein foldin)
Protein synthesis
appens in the ri(osome
4in'ed (" peptide (ond 7C5N8
lwa"s unidire+tional: from N5terminal to C5terminal)
9he primar" ri(osome produ+t is a pol"peptide +hain)o lwa"s 1
ene 1 m.N s"nthesis of pol"peptide +hains
o 20 natural amino a+ids
"drophili+
"dropho(i+
+idi+
asi+
Sulpher5+ontainin
o Non5natural amino a+ids
Can (e used as pro(es
Perhaps in spe+ial drus)
Protein Structure
Primar": the amino a+id se/uen+e)
Se+ondar" : the ; stru+ture, 5heli+es, ?5sheets, and
re#erse turns)
9ertiar" : the ; +onfiuration and how it fits with other
proteins)
@uaternar" : intera+tion (etween pol"peptide +hain su(unitsA for
example,
homodimers 7sinle su(units8 and heterodimers
7multi5su(units8)
omains: the tertiar" or se+ondar" stru+ture
Compa+t lo(ular unit whi+h +ontains the fun+tional part of a
protein)
Ma" point toward eneti+ and +ellular heredit" of proteins)
Motif: se/uen+es not asso+iated with stru+ture
Pol"peptide se/uen+es that are asso+iated with fun+tion)
Note: domains and motifs are shared a+ross a famil" of
proteins)
2
Good test question:
Can proteinss"nthesi&e from (oth
N5terminal to C5
terminal
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8/13/2019 Mutations and SNPs
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Experimental Methods Class Notes June 6, 2001
*ou +an predi+t motifs from se/uen+es, (ut it is hard to predi+t
domains)
Posttranslational !odifications
Proteol"ti+ pro+essin 7e)) (lood +lottin8
o Bor se+retionleader peptides
o na+ti#e to a+ti#e en&"me: &"moensinsulin
Proteol"ti+all" pro+essed, these en&"mes ha#e different
+ellDoran
sour+es)
o iral assem(l": #iral m.N to protein is pro+essed (" #iral
proteases)
o Pol"peptide spli+in: +an+a#alin , final pol"peptide is a
spli+ed #ariant
of the oriinal)
o lteration of +hain termini
N5terminal met is atta+hed with a form"l roup)
+et"lation of N5terminus
!l"+os"l5phosphate mem(rane an+hors atta+h to +ell mem(ranes
of solu(le proteins)
9he followin t"pes of +hanes +an (e predi+ted:
!l"+os"lation
o N5lin'ed: mostl" in E).) and on sn
o F5lin'ed: SerD9hr in oli (odies
4ipid atta+hment: to tether solu(le proteins to mem(ranes
o E)) m"ristol, palmito"l, et+)
Phosphor"lation
o Primaril" at F roups of Ser, 9hr, or 9"r
isulphide (ond formation: (onds (etween two +"stines
Why deter!ine protein structure?
Stru+ture determines fun+tion
enotes relationships (etter than se/uen+e
Small mole+ules often alter protein fun+tion (" alterin lo+al
stru+tures
;
