BMB170 2017 Lecture2 - California Institute of...
Transcript of BMB170 2017 Lecture2 - California Institute of...
!"!#$%&'()*+,-. !/+0*1(+&23&4+5*6&27*8
• 4+0)-9:(;&.*(10*1(+&– .*:<,=,>:?)-&– @A8+=,B&CD+(:?-3&E;).,-F&– GA.8++*.&C.,=DF&– 0)==:H+-&
• I+(?:(;&4*(10*1(+
'+5?9+.&:-9&8;9()H+-&<)-9,-H• J;9()H+-&<)-9.&)001(&<+*K++-&:&
!)-)(&:-9&"00+5*)(&– LAJMMMMMN&K8+(+&L&O&N&:(+&*;5,0:==;&
P3&Q&C4F&– !:0D<)-+&,-&.+0)-9:(;&.*(10*1(+&
PAJMMMMMMMMQRS&• L,.*:-0+&26TAU6TV&NAL&• S)-*(,<1*+.&WUD0:=XE)=+&CW#%%B&
.E:==+(&*8:-&:&0)Y:=+-*&<)-9F&• N==&8;9()H+-&<)-9.&E1.*&<+&
.:?.Z+9&C+,*8+(&,-*(:E)=+01=:(&)(&<;&.)=Y+-*F
2.8Å
C!
HN
CO
C!NH
OC
C!NH
OC
C!
HN
CO
[+.*(,0*+9&*)(.,)-&:-H=+.&
+B*+-9+9&5)=;5+5?9+&08:,-&!, "&R%\
Ca
C
NH
Ca
C
HN
Ca
O
O
!
"
A
B C
DA
B,C
D!
!
!"#$%"&'(&)*+',+-&%."&'
5+(E,..,<=+&!,"&Y:=1+.&:(+&+-+(H+?0:==;&]:Y)(:<=+&*)(.,)-&:-H=+.&K,*8&<:9&0)-*:0*.&:(+&9,.]:Y)(+9
])(&-)-A<)-9+9&&&& S^^^S&H()15.&_E,-&W%6#&A&%67&D`XE)=+&[E,-&W&U67&V
I)(.,)-&:-H=+&(+.*(,0?)-.
-2
0
2
4
6
8
10
3 4 5 6 7 8
separation (Å)
en
erg
y (
kJ/
mo
le)
methane
argon
U R( ) =AR12
"BR6
= Emin "RminR
#
$ %
&
' ( 12
+ 2 RminR
#
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,
- .
a6P6&[:E:08:-9(:-
"
#
[:E:08:-9(:-&!"#$%&#$%&C#bcUF&$3&bTAb
[:E:08:-9(:-&'=)* !:==)K+9&*)(.,)-&:-H=+.&)]&*8+&
5)=;5+5?9+&08:,- !
ddd&Q/L&SQPe_PIfQP&gQ[&NPa/_4
.++&J)&!"#$%&&'()*+,-*C2%%UF#2h2T%7
[:E:08:-9(:-&E)(+&(+Z-+9
i+&1.+&*8,.&0)-Y+-?)-6
a=; '()
58,
5.,
P)-Aa=;3'()
8j5hXXB(:;6<E06116.+XH+(:(9X.15E:*X-)-H=;5()k(:E56H,]
[:E:08:-9(:-&5=)*
J)&!"#$%&&'()*+,-*C2%%UF#2h2T%7
0:-&:=.)&8:Y+&0)15=,-H&)]&E:,-08:,-X.,9+08:,-&*)(.,)-&:-H=+.&S8:D(:<:(?&O&':=&'()H&!,)58;.&")=&!,)=&C2%%#F$ch#
4,9+&08:,-&*)(.,)-&:-H=+.&C()*:E+(.F!&&&##&9+.0(,<+.&()*:?)-&:<)1*&*8+&S$AS%&<)-9
H
H C!
C"
N
COH
C!
H H
C"
N
COH
H
C! H
C"
N
COH
#1 = +60˚least pop.
g-
#1 = 180˚intermed.
trans
#1 = -60˚
favoredg+
'&R&5,*08&C(+5+:*&9,.*:-0+&:=)-H&8+=,BF&
9&R&(,.+&5+(&(+.,91+&:=)-H&8+=,B&
-&R&-1E<+(&)]&(+.,91+.&,-&)-+&8+=,0:=&*1(-&
&&R&()*:?)-&:-H=+&5+(&(+.,91+&:=)-H&8+=,B&&&&&&C-)*+h&*8,.&&&,.&9,l+(+-*&*8:-&*8+&&&&&&&&5+5?9+&<)-9&5=:-:(,*;&*)(.,)-&:-H=+F&
'&R&9^-&
&R&Uc%\X-
L,0D+(.)-&O&a+,.3&&"'()"('!#$*+#,)-.*#./#0'."!1*2#C#bcbF
N==)K+93&(+H1=:(&.*(10*1(+.&C.+0)-9:(;&.*(10*1(+.F&
(+5+:*+9&!,"&Y:=1+.&,-&:==)K+9&(+H,)-.&)]&[:E:08:-9(:-&5=)*
[+=:?)-.8,5&<+*K++-&!, "&:-9&93-
.
. /01.201.
/01.
201.
L,0D+(.)-&O&a+,.3&&"'()"('!#$*+#,)-.*#./#0'."!1*2#C#bcbF
cos "2#
$ %
&
' ( = +0.817sin ) +*
2#
$ %
&
' ( + 0.045sin
) +*2
#
$ %
&
' (
d sin "2#
$ %
&
' ( = +2.967cos
) +*2
#
$ %
&
' ( + 0.664cos
) +*2
#
$ %
&
' (
" = 360˚/n
!,)=)H,0:=&8+=,0+.
'PN4&C#bT#F&U$h2%TA2##
I8+&$A8+=,B
J+(E:-&!(:-.)-
• e,.,?-H&5()]+..)(&]()E&J)K:(9&m-,Y+(.,*;&• g()E&i,D,5+9,:h&
– In 1984 Branson wrote Pauling biographers Victor and Mildred Goertzel implying that his
contribution to the !-helix had been greater than the final paper indicated. “I took my work to Pauling who told me that he thought they [the proposed alpha and gamma helixes] were too tight, that he thought that a protein molecule should have a much larger
radius so that water molecules could fit down inside and cause the protein to swell,” he wrote. “I went back and worked unsuccessfully to find such a structure.” When he received Pauling’s note with the draft manuscript, Branson wrote, “I interpreted this letter as establishing that the ! and " in my paper were correct and that the subsequent work done was cleaning up or verifying. The differences were nil.” He added in his letter to the Goertzels that he “resented” the later attention lavished on Pauling and Corey.[4] The conservative watchdog group Accuracy in Media referred to the incident in an attack on Pauling in 1994.[5] The available records, historical context, knowledge of the personalities involved, and studies of Pauling's laboratory and methods at the time have led most historians to accord greater credit to Pauling and Corey.[6][7]
33$4
5
6
':1=,-H&:-9&S)(+;&S'n
[,H8*&J:-9+9&)(
/+o&J:-9+9
p':1=,-Hq.&/+oAJ:-9+9&J+=,Br&&`L&L1-,*>&,*3!45#67!85#9*"%5#!+6&C2%%#F&s%hs#c$
p[,08:(9& ":(.83& )-+& )]& *8+& ]+K& .1(Y,Y,-H&0(;.*:==)H(:58+(.& ]()E& *8:*& a)=9+-& NH+& ,-&.*(10*1(:=& 08+E,.*(;& :*& S:=*+083& 8:.& +B5=:,-+9& *)&E+& *8:*& :*& *8:*& ?E+& *8+& S:=*+08& H()15& K+(+&,-*+(+.*+9& ,-& 9+*:,=.& )]& E)=+01=:(& .*(10*1(+3& ,-&<)-9& =+-H*8.& :-9& <)-9& :-H=+.3& ,-& ,-*+(:*)E,0&9,.*:-0+.3& ,-&]+:*1(+.&*8:*&K+(+&t1.*&:.&(+=+Y:-*& ,-&:& =+oA8:-9+9& K)(=9& :.& ,-& :& (,H8*A8:-9+9& )-+6& f*&K:.&,-9++9&*8+&0=).+&:j+-?)-&*)&.108&9+*:,=.&*8:*&:==)K+9&':1=,-H&,-&*8+&Z(.*&5=:0+&*)&<1,=9&E)9+=.&)]&5)=;5+5?9+& 08:,-.& *8:*& K)1=9& .:?.];& *8+& .*(,0*&.*(10*1(:=& (+u1,(+E+-*.& *8:*& 8:9& +E+(H+9& ]()E&.108& .*19,+.6& '()<=+E.& )]& :<.)=1*+& 0)-ZH1(:?)-&(+0+,Y+9& =,j=+& )(& -)& :j+-?)-& <+0:1.+& *8+(+&.++E+9&*)&<+&-)&-++9&])(&*8+E&*8+-6&'+(8:5.&*8+;&K+(+&+Y+-&(+H:(9+9&:.&:&9,.*(:0?)-&]()E&*8+&*:.D&:*&8:-96&4)E+?E+.&)-+&0:-&])01.&E)(+&0=+:(=;&<;&0=).,-H&)-+&+;+6r
':1=,-Hq.&8+=,B
!:.,0&]+:*1(+.&)]&*8+&$A8+=,B• JA<)-9&<+*K++-&SQ&)]&(+.,91+&,&O&PJ&)]&,vs&• S$AS%&<)-9&5),-*.&*)K:(9.&*8+&PA*+(E,-1.&
– S8(,.*E:.&*(++&?5&,.&SA*+(E,-1.&• NY+(:H+&=+-H*8&W#2&(+.,91+.&CK:*+(A.)=1<=+&
5()*+,-.F&• m-.:?.Z+9&JA<)-9.&:*&+-9.&• P+*&9,5)=+&:*&+-9.&
– N==&JA<)-9.&5),-*&,-&.:E+&9,(+0?)-&– S:-&.*:<,=,>+&8+=,B&8+=,B&5:0D,-H&– S:-&0)-*(,<1*+&*)&:0?Y+&.,*+&
• 4,9+&08:,-.&0:-&:l+0*&8+=,0+.
P&CWv%6TF
S&CWA%6TF
-& 9& &&& '& && & ! "&U6c& #6TV& T6sV& #%%\& AT$\&As$\
'())]&*8+;&K+(+&(,H8*&w&":B&'+(1*>
• I8+&':1=,-H&E)9+=&5(+9,0*+9&:TV&(+x+0?)-&
• P)-+&8:9&.++-&,*y
":B&'+(1*>&C#bb$Fh&i8+-&f&.:K&*8+&:=58:&8+=,B&:-9&.:K&K8:*&:&<+:1?]1=&+=+H:-*&.*(10*1(+& ,*&K:.3& f&K:.&*81-9+(.*(10D&:-9&K:.& ]1(,)1.&K,*8&E;.+=]& ])(&-)*&8:Y,-H&<1,=*& *8,.3&<1*&)-& *8+&)*8+(&8:-9&f&K)-9+(+93&K:.&,*&(+:==;&(,H8*z&4)&f&.*:(*+9&8)E+&])(& =1-08& :-9& K:.& .)& 5(+)0015,+93& *8+& *1(E),=& ,-& E;& E,-9&*8:*& 9,9-{*& (+.5)-9& *)& :-;*8,-H6& I8+-& f& 8:9& :-& ,9+:3& .)& f&.*:(*+9&<:0D&*)&*8+&=:<6& f&(+:=,>+9&*8:*&f&8:9&:&8)(.+&8:,(& ,-&:&9(:K+(6& f& .+*& ,*&15& ])(& *8+&BA(:;& 0:E+(:&:-9&H:Y+& ,*& :&2&8)1(&+B5).1(+3&*8+-&*))D&*8+&Z=E&*)&*8+&9:(D&())E&K,*8&E;&8+:(*&,-& E;& E)1*83& K)-9+(,-H& K8:*& ,*& .8)K+93& :-9& K8+-& f&9+Y+=)5+9& ,*3& *8+(+& K:.& *8+& #6TV& (+x+0?)-& K8,08& f& 8:9&5(+9,0*+9& :-9& K8,08& +B0=19+9& :==& .*(10*1(+.& )*8+(& *8:-& *8+&:=58:A8+=,B6& 4)& )-& ")-9:;& E)(-,-H& f& .*)(E+9& ,-*)& E;&5()]+..)({.& )|0+3& ,-*)& !(:HH{.& )|0+& :-9& .8)K+9& 8,E& *8,.3&:-9&!(:HH&.:,93&}i+==3&K8:*+Y+(&E:9+&;)1&*8,-D&)]&*8:*z}&N-9&f&.:,93&}i+==3&<+0:1.+&f&K:.&.)&]1(,)1.&K,*8&E;.+=]&])(&8:Y,-H&E,..+9& ,*6}&I)&K8,08&!(:HH&(+5=,+9&0)=9=;3&}f&K,.8& f&8:9&E:9+&;)1&:-H(;&+:(=,+(6r
L,0D+(.)-&O&a+,.3&&"'()"('!#$*+#,)-.*#./#0'."!1*2#C#bcbF
!,)=)H,0:=&'()*+,-&J+=,0+.
_E<+(=;&!"#$%&`"!&C2%%UFU2$h22b _-H+=&O&L+a(:9)&`"!&C2%%sFUU$h##bT
L,.*)(?)-.&*)&8+=,0+.
J+=,B&x+B,<,=,*;P)-A(:-9)E&8+=,B&=+-H*8&9,.*(,<1?)-
!+-9 IK,.*
J+=,B&+-9.
• Qo+-&8+=,0+.&:(+&0:55+9&:*&*8+,(&PA*+(E,-,&
• '()=,-+.&)o+-&1.+9&*)&<(+:D&8+=,0+.
n+(:?-&4*(10*1(+• I8+&5()<=+E&K,*8&*8+&T6#V&(+x+0?)-&• ':1=,-H&<:.,0:==;&,H-)(+9&,*&
– @A8+=,B&,.&T6sV&– H1+..+9&,*&0)1=9&<+&91+&*)&:&*(,5=+&8+=,B&
• g(:-0,.&S(,0D&– P:*1(+&C#bT2F&#$%h772&– #6TV&(+x+0?)-&w&,*&,.&:&8+=,B&– n+(:?-&,.&:&0),=+9A0),=&– I,=*&,*~&CT6s&).2#7&R&T6#F&– N&.15+(&8+=,B�
L,0D+(.)-&O&a+,.3&&"'()"('!#$*+#,)-.*#./#0'."!1*2#C#bcbF
J+=,BA8+=,B&5:0D,-H&&&
4*:<,=,>+9&<;&.,9+08:,-A.,9+08:,-&,-*+(:0?)-.&)o+-&,-Y)=Y,-H&0)-*:0*.&<+*K++-&:5)=:(&(+.,91+.
W7A#%&V
I+(?:(;&.*(10*1(+h !':0D,-H&*)H+*8+(&)]&.+0)-9:(;&.*(10*1(+&+=+E+-*.
S%&(+5(+.+-*:?)-&)]&$A8+=,B
[,9H+.&0:1.+9&<;&.,9+&08:,-.&.+5:(:*+9&<;&s&(+.,91+.&&&&)(&&&&U&(+.,91+.
g,H6&U6##3&!(:-9+-&:-9&I))>+&S8)*8,:&!"#$%&'PN4&C#b$$F&$sh#%&55s#U%As
J+=,B&':0D,-H
s&(+.,91+&&(,9H+.
s&(+.,91+&&(,9H+.
I1(-&)Y+(&J+=,B&ff
[)*:*+&T%\&*)&5:0D&(,9H+.&,-*)&
H())Y+.
s&(+.,91+&&(,9H+.
U&(+.,91+&&(,9H+.
I1(-&)Y+(&J+=,B&ff
[)*:*+&2%\&*)&5:0D&(,9H+.&,-*)&&
H())Y+.
g,H6&U6#23&!(:-9+-&:-9&I))>+&S8)*8,:&!"#$%&'PN4&C#b$$F&$shs#U%
g,H.6&U6c&:-9&U6$3&!(:-9+-&:-9&I))>+
N9t:0+-*&8+=,0+.&:-?5:(:==+=
IK)&5:,(.&)]&5:(:==+=&8+=,0+.&t),-+9&*)&E:D+&:-?5:(:==+=&<1-9=+
J;9()58)<,0&,-*+(,)(
S()..,-H&:-H=+&(+.1=*.&]()E&(,9H+.&,-*)&H())Y+.&5:0D,-H
g)1(&8+=,B&<1-9=+.
&[+H1=:(&.+0)-9:(;&.*(10*1(+.&-)*&.*:<,=,>+9&<;&8;9()H+-&<)-9.&<+*K++-&-+:(<;&(+.,91+.
'PN4&C#bT#F&U$h$2b
I8+&%A.8++*
&'R&c67&V
_B*+-9+9&5)=;5+5?9+&08:,-&C%A.*(:-9F
• p>,HA>:Hr&:55+:(:-0+&• '+5?9+&<)-9.&)]&:9t:0+-*&(+.,91+.&5),-*&,-&)55).,*+&9,(+0?)-.&• N=*+(-:*+&.,9+08:,-.&+B*+-9&)-&)55).,*+&.,9+.&)]&.*(:-9
N-?A5:(:==+=&&
%A.8++*
-& &&9& &&& &&&'& &&& &&&&& & &&&!& & &&&"&26%& U6sV& c67V& #7%\& A#Ub\& v#UT\& g,H.6&26T3&!(:-9+-&:-9&I))>+
Ws6TV
':(:==+=&%A.8++*
&-& &&9& &&& &&&&'& &&&& &&&& ! "&26%& U6sV& c67V& %\& A##b\& &&v##U\& g,H.6&26c3&!(:-9+-&:-9&I))>+
C1X9&R&15X9)K-F _E<+(=;&!"#$%5#'()*+,-.&C2%%sF&TThb#
",B+9&.8++*.&:(+&.*:?.?0:==;&=+..&=,D+=;
• ])(&c&.*(:-9+9&.8++*&– g,B&)-&Z(.*&.*(:-9&– U2&9,l+(+-*&H+)E+*(,+.&&
• (:-9)E&9,.*(,<1?)-&– +B5+0*&UT#cXU2&&– W##%&+B:E5=+.&)]&+:08
[,H8*&8:-9+9&:=)-H&.*(:-9.&,-&08:,-&9,(+0?)-&
/+o&8:-9+9&'&&*)&.*(:-9.&
S8)*8,:&`"!&C#b$UF&$Th2bT
%A.8++*.&8:Y+&:&08:(:0*+(,.?0&*K,.*
L,.*)(?)-&,-&.8++*.&0:-&<+&*K,.*.&)(&<+-9.&
N-?A5:(:==+=&*+-9&*)&<+&E)(+&9,.*)(*+9&
_E<+(=;&!"#$%5#'()*+,-.&C2%%sF&TThb#
/))5&0)--+0?)-.&<+*K++-&:9t:0+-*&:-?A5:(:==+=&%A.*(:-9.
2&[+.,91+.&5(+9)E,-:-*
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I;5+&f&I1(-I;5+&ff&I1(-
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-
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-/8 -
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4,=D&4*(10*1(+
• 4,=D&,.&5:0D+9&GA.8++*&• N=*+(-:?-H&.+u1+-0+&)]&AH=;A:=:AH=;A:=:A&
• 2&.+5:(:*+&.5:0,-H.&• P+:(=;&]1==;&+B*+-9+93&-)*&E108&H,Y+&
• 4+u1+-0+&Y:(,:-*.&:=*+(&5=,:<,=,*;
L,0D+(.)-&O&a+,.3&&"'()"('!#$*+#,)-.*#./#0'."!1*2#C#bcbF
!=:D+&O&4+(5+==&4*(10*1(+&C#bbcF&shb7b&P+=.)-&!"#$%5#P:*1(+&C2%%TF&sUTh$$U
%A.8++*.&:-9&:E;=),9&Z<(,=.
Scurvy• Jacques Cartier (1536) “Some did lose
all their strength, and could not stand on their feet…. Others also had all their skins spotted with spots of blood of a purple colour: then did it ascend up to their ankles, knees, thighs, shoulders, arms, and necks. Their mouths became stinking, their gums so rotten, that all the flesh did fall off, even to the roots of the teeth, which did also almost all fall out”&
• In 1865 British Sailors were given limes to help combat the disease leading to the nickname ‘limeys’
Collagen• 25% of the protein in your body
is collagen&• Used in basic cell structure&
– Tendons&– Organelle structure&– Bones/teeth (forms basal matrix)&
• Composed of three chains forming a triple helix&– ~1400aa&– Every third residue is Gly&– -Pro-Hyp-Gly-
!:.+E+-*&E+E<(:-+.&)]&E:-;&)(H:-+==+.&CfeF
Collagen Structure (1bkv)• Repeating unit forms stable packing&• Hydroxyproline essential for regular
packing&– prolyl hydroxylase uses ascorbic acid (vitamin
C) to add oxygen&– Extra hydrogen bond stabilizes from 24C to
58C?&– Hydroxyl is electron withdrawing stabilizing
the triple helix conformation (Raines lab, Wisconsin)&
• ')=;5()=,-+&ff&=+oA8:-9+9&8+=,B&– -&R&U&Ä&9&R&U6#&VÄ&&&R&A#2%\&– C!,"F&R&CA$T\3&#T%\F
'()
J;5
a=;
n(:E+(&!"#$%&P:*1(+&4*(10*&!,)=&C#bbbF&chsTsA$
WbV
WbV&R&2&B&s6T&V
$A8+=,BX&%A.8++*&4*(10*1(+.
g,H6&26#73&!(:-9+-&:-9&I))>+
[,H8*A8:-9+9 /+oA8:-9+9
%$%&E)?].&,-&.*(10*1(+.&0)-*:,-,-H&5:(:==+=&%A.8++*.
• N9t:0+-*&5:(:==+=&%A.*(:-9.&1.1:==;&0)--+0*+9&<;&:-&$A8+=,B&
• J+=,0:=&:B,.&,.&:=E).*&5:(:==+=&*)&.*(:-9.&
• N=E).*&:==&0)--+0?)-.&:(+&(,H8*A8:-9+9&ÅbTÇ