Sickle Cell Anemia Project

Computational Molecular Biology

by
Michael Smith
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Step 1 : Obtain an overview of ickle cell anemia
The first step of this project involved obtaining an overview of sickle cell anemia and in
the process familiarizing myself with the condition. By performing a Google
(www.google.com) search with the key words sickle cell anemia, came across
the websites of the The Sickle Cell Information Center at !mory
"niversity (www.scinfo.org) and The Sickle Cell Disease Association
of America (http#$$www.sicklecelldisease.org). Both sites contain a wealth of
information, abo%t sickle cell anemia, and relevant e&erts are presented below.

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Sickle Cell Anemia Overview
'ickle cell disease is an inherited blood disorder that affects red blood cells.
(eople with sickle cell disease have red blood cells that contain mostly hemoglobin) ',
an abnormal type of hemoglobin. 'ometimes these red blood cells become sickle*shaped
(crescent shaped) and have diffic%lty passing thro%gh small blood vessels.
+hen sickle*shaped cells block small blood vessels, less blood can reach that part
of the body. Tiss%e that does not receive a normal blood flow event%ally becomes
damaged. This is what ca%ses the complications of sickle cell disease. There is c%rrently
no %niversal c%re for sickle cell disease.
Hemoglobin is the main s%bstance of the red blood cell. t helps red blood cells
carry o&ygen from the air in o%r l%ngs to all parts of the body. ,ormal red blood cells
contain hemoglobin -. .emoglobin ' and hemoglobin / are abnormal types of
hemoglobin. ,ormal red blood cells are soft and ro%nd and can s0%eeze thro%gh tiny
blood t%bes (vessels). ,ormally, red blood cells live for abo%t 123 days before new ones
replace them.
(eople with sickle cell conditions make a different form of hemoglobin - called
hemoglobin ' (' stands for sickle). 4ed blood cells containing mostly hemoglobin ' do
not live as long as normal red blood cells (normally abo%t 15 days). They also become
stiff, distorted in shape and have diffic%lty passing thro%gh the body6s small blood
vessels. +hen sickle*shaped cells block small blood vessels, less blood can reach that
part of the body. Tiss%e that does not receive a normal blood flow event%ally becomes
damaged. This is what ca%ses the complications of sickle cell disease.
7o% inherit the abnormal hemoglobin from yo%r parents, who may be carriers
with sickle cell trait or parents with sickle cell disease. 7o% can not catch it. 7o% are born
with the sickle cell hemoglobin and it is present for life. f yo% inherit only one sickle
gene, yo% have sickle cell trait. f yo% inherit two sickle cell genes yo% have sickle cell
disease.
'ickle cell trait is a person who carries one sickle hemoglobin prod%cing gene
inherited from their parents and one normal hemoglobin gene. ,ormal hemoglobin is
called type -. 'ickle hemoglobin called '. 'ickle cell trait is the presence of hemoglobin
-' on the hemoglobin electrophoresis. This will ,8T ca%se sickle cell disease. 8ther
hemoglobin traits common in the "nited 'tates are -/ and -! traits.
- simple blood test followed by a laboratory techni0%e called Hemoglobin
Electrophoresis will determine the type of hemoglobin yo% have. +hen yo% pass an
electric charge thro%gh a sol%tion of hemoglobin, distinct hemoglobins move different
distances, depending on their composition. This techni0%e differentiates between normal
hemoglobin (-), 'ickle hemoglobin ('), and other different kinds of hemoglobin (s%ch as
/, 9, !, etc.).
'ickle cells are destroyed rapidly in the body of people with the disease ca%sing
anemia, ja%ndice and the formation of gallstones. The sickle cells also block the flow of
blood thro%gh vessels res%lting in l%ng tiss%e damage (ac%te chest syndrome), pain
episodes (arms, legs, chest and abdomen), stroke and priapism (painf%l prolonged
erection). t also ca%ses damage to most organs incl%ding the spleen, kidneys and liver.
9amage to the spleen makes sickle cell disease patients, especially yo%ng children, easily
overwhelmed by certain bacterial infections.
.ealth maintenance for patients with sickle cell disease starts with early
diagnosis, preferably in the newborn period and incl%des penicillin prophyla&is,
vaccination against pne%mococc%s bacteria and folic acid s%pplementation.
Treatment of complications often incl%des antibiotics, pain management, intraveno%s
fl%ids, blood transf%sion and s%rgery all backed by psychosocial s%pport. :ike all patients
with chronic disease patients are best managed in a comprehensive m%lti*disciplinary
program of care.
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Step ! : Obtain information on the gene reponible for ickle cell anemia
The second step of this project involved information specifically on the gene responsible
for sickle cell anemia. 'imilar to 'tep 1, this step involved a ;oogle search b%t this time
with the key words sickle cell gene. The websites of The Oak Ride
National Laboratory (www.ornl.gov ) and The Centers of Disease
Control (www.cdc.gov) were of great %se for obtaining the needed information.
________________________________________________________________________
Sickle Cell "ene #nformation
Official "ene Symbol: .BB
$ame of "ene Pro%uct: hemoglobin, beta
Alternate $ame of "ene Pro%uct: beta globin
&ocu: 11p1<.< The .BB gene is fo%nd in region 1<.< on the short (p) arm of h%man
chromosome 11.
Si'e: The .BB gene=s > coding regions (e&ons) are scattered over 1533 base pairs of
genomic 9,-. !&ons translated into the .BB polypeptide chain are interspersed with
segments of noncoding 9,- (introns). -fter transcription, introns are spliced o%t and
e&ons are pieced together to form a 525*bp m4,- transcript that is translated into the
1?@*amino acid se0%ence of the .BB polypeptide chain.
m($A e)uence
1 ACATTTGCTT CTGACACAAC TGTGTTCACT AGCAACCTCA AACAGACACC ATGGTGCATC
61 TGACTCCTGA GGAGAAGTCT GCCGTTACTG CCCTGTGGGG CAAGGTGAAC GTGGATGAAG
121 TTGGTGGTGA GGCCCTGGGC AGGCTGCTGG TGGTCTACCC TTGGACCCAG AGGTTCTTTG
181 AGTCCTTTGG GGATCTGTCC ACTCCTGATG CTGTTATGGG CAACCCTAAG GTGAAGGCTC
241 ATGGCAAGAA AGTGCTCGGT GCCTTTAGTG ATGGCCTGGC TCACCTGGAC AACCTCAAGG
301 GCACCTTTGC CACACTGAGT GAGCTGCACT GTGACAAGCT GCACGTGGAT CCTGAGAACT
361 TCAGGCTCCT GGGCAACGTG CTGGTCTGTG TGCTGGCCCA TCACTTTGGC AAAGAATTCA
421 CCCCACCAGT GCAGGCTGCC TATCAGAAAG TGGTGGCTGG TGTGGCTAAT GCCCTGGCCC
481 ACAAGTATCA CTAAGCTCGC TTTCTTGCTG TCCAATTTCT ATTAAAGGTT CCTTTGTTCC
541 CTAAGTCCAA CTACTAAACT GGGGGATATT ATGAAGGGCC TTGAGCATCT GGATTCTGCC
601 TAATAAAAAA CATTTATTTT CATTGC
Amino Aci% Se)uence *+BB,
M 1 VHLTPEEKS AVTALWGKVN VDEVGGEALG RLLVVYPWTQ RFFESFGDLS TPDAVMGNPK
60 VKAHGKKVLG AFSDGLAHLD NLKGTFATLS ELHCDKLHVD PENFRLLGNV LVCVLAHHFG
120 KEFTPPVQAA YQKVVAGVAN ALAHKYH
,ote# The first AUG is translated as methionine m! b%t that amino acid is removed
from the polypeptide chain and the ne&t amino acid, "aline "!# is the first amino
acid in the mat%re polypeptide chain.
'ickle cell disease is ca%sed by a variant of the A*globin gene called sickle
hemoglobin (Hb S ). nherited a%tosomal recessively, either two copies of Hb S or one
copy of Hb S pl%s another A*globin variant (s%ch as Hb C) are re0%ired for disease
e&pression.
The A*globin gene is located on the short arm of chromosome 11. t is a member
of the globin gene family, a gro%p of genes involved in o&ygen transport. 8ther members
of this gene family incl%de the B*, C*, D* E*, and F*globin genes. The globin genes are
developmentally reg%lated, s%ch that certain genes are e&pressed at specific times d%ring
h%man development. Two A Gglobin protein chains combine with two B *globin protein
chains and a heme to form the predominant hemoglobin (.b) fo%nd in h%man ad%lts.
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Step - : Obtain known gene variant
The third step of this project involved searching for known gene variants or m%tations of
the gene responsible for sickle cell anemia (.BB). 'imilar to the two preceding steps, a
;oogle search was e&ec%ted with the key words sickle cell gene "ariants.
The websites of the Centers of Disease Control and the Gene Globin
Center of (ennsylvania 'tate "niversity (globin.cse.ps%.ed%) were of great val%e in
obtaining this information.
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.nown "ene /ariant *Mutation,
8ver ?@< A*globin gene variants e&ist, and several res%lt in life*threatening illness.
0ith repect to the ickle cell *Hb S) variant1 the molecular nature i a ubtitution
of valine for glutamic aci% at the i2th amino aci% poition in the 34globin gene.
ndivid%als of -frican descent e&hibit the highest fre0%ency of at*risk genotypes
associated with Hb S. .owever, individ%als of Hediterranean, /aribbean, 'o%th and
/entral -merican, -rab, and !ast ndian descent also e&hibit high fre0%encies of at*risk
genotypes
The following table presents known variations of the .BB gene that involve single base
changes. 8nly ten e&amples are presented, however h%ndreds e&its and complete list can
be fo%nd at the website of the ;ene ;lobin /enter.

.nown variation of the +BB gene *ingle bae change,
+b $ame (ei%e $umber Amino Aci% Subtitution "ene Mutation
9eer :odge 2 .is*I-rg /-/*I/;/
' 5 ;l%*IJal ;-;*I;T;
7%sa 21 -sp*ITyr ;-T*IT-T
7okohama >1 :e%*I(ro /T;*I//;
-rta ?< (he*I/ys TTT*IT;T
7ats%shiro 53 Jal*I:e% ;T;*I/T;
Kof% L? Thr*Ile -//*I-T/
9jelfa ML Jal*I-la ;T;*I;/;
+ien 1>3 Tyr*I-sp T-T*I;-T
Kodaira 1?5 .is*I;ln /-/*I/--
The following table presents known variations of the .BB gene that involve m%ltiple
base changes. 8nly ten e&amples are presented, however a complete list can be fo%nd at
the website of the ;ene ;lobin /enter.
.nown variation of the +BB gene *multiple bae change,
+b $ame (ei%e $umber Amino Aci% Subtitution "ene Mutation
'*-ntilles 5 ;l%*IJal ;-;*I;T;
2> Jal*Ile ;TT*I-TT
/*Ni0%inchor 5 ;l%*IJal ;-;*I;T;
<L (ro*I-rg //T*I/;T
/*.arlem 5 ;l%*IJal ;-;*I;T;
@> -sp*I-sn ;-T*I--T
'*(rovidence 5 ;l%*IJal ;-;*I;T;
L2 :ys*I-sn*I-sp --;*I--T or --/
'*8man 5 ;l%*IJal ;-;*I;T;
121 ;l%*I:ys ;--*I---
'*Travis 5 ;l%*IJal ;-;*I;T;
1?2 -la*IJal ;//*I;T/
-rlington (ark 5 ;l%*I:ys ;-;*I--;
M< :ys*I;l% --;*I;-;
T*/ambodia 25 ;l%*I:ys ;-;*I--;
121 ;l%*I;ln ;--*I/--
;renoble <1 (ro*I'er //T*IT/T
<2 -sp*I-sn ;-T*I--T
(oissy <5 ;ly*I-rg ;;/*I/;/
L5 -la*I(ro ;//*I///
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Step 5 : Protein Secon%ary Structure Pre%iction
'tep fo%r involves predicting the secondary str%ct%re of proteins that are prod%ced by the
normal and m%tated genes. The tables in the preceding section detail the changes in the
amino acid se0%ences as a res%lt of gene m%tation. These amino acid se0%ences were fed
into the SS$ro protein secondary prediction system
(http#$$www.igb.%ci.ed%$tools$scratch$)
+BB Se)uence an% Pre%icte% Secon%ary Structure
Pri. Sr!"!r# $ VHLTPEEKSAVTALWGKVNVDEVGGEALGRLLVVYPWTQRFFESFGDLSTPDAVMGNPKV
S#". Sr!"!r# $ CCCCHHHHHHHHHHHCCCCHHHHHHHHHHHHHEECHHHHHHHHHCCCCCCHCHHCCCCCH
Pri. Sr!"!r# $ KAHGKKVLGAFSDGLAHLDNLKGTFATLSELHCDKLHVDPENFRLLGNVLVCVLAHHFGK
S#". Sr!"!r# $ HHCHHHHHHHHHHHHHHHHHHHHHHHHHHHHCCCCCCCCHHHHHHHHHHHHHHHHHHHCC
Pri. Sr!"!r# $ EFTPPVQAAYQKVVAGVANALAHKYH
S#". Sr!"!r# $ CCCHHHHHHHHHHHHHHHHHHHHHCC
The following m%tated se0%ences have predicted secondary str%ct%res e0%al to that of the
.BB se0%ence. (The m%tated amino acids are in bold font)
,ote # 4ecall the .BB se0%ence is that prod%ced by normal (non*m%tated) genes
Hb S
1 VHLTPVEKS AVTALWGKVN VDEVGGEALG RLLVVYPWTQ RFFESFGDLS TPDAVMGNPK
60 VKAHGKKVLG AFSDGLAHLD NLKGTFATLS ELHCDKLHVD PENFRLLGNV LVCVLAHHFG
120 KEFTPPVQAA YQKVVAGVAN ALAHKYH
Hb Yusa
1 VHLTPEEKS AVTALWGKVN VYEVGGEALG RLLVVYPWTQ RFFESFGDLS TPDAVMGNPK
60 VKAHGKKVLG AFSDGLAHLD NLKGTFATLS ELHCDKLHVD PENFRLLGNV LVCVLAHHFG
120 KEFTPPVQAA YQKVVAGVAN ALAHKYH
Hb Deer Lodge Sequence
1 VRLTPEEKS AVTALWGKVN VDEVGGEALG RLLVVYPWTQ RFFESFGDLS TPDAVMGNPK
60 VKAHGKKVLG AFSDGLAHLD NLKGTFATLS ELHCDKLHVD PENFRLLGNV LVCVLAHHFG
120 KEFTPPVQAA YQKVVAGVAN ALAHKYH
Hb Yokohama
1 VHLTPEEKS AVTALWGKVN VDEVGGEALG RPLVVYPWTQ RFFESFGDLS TPDAVMGNPK
60 VKAHGKKVLG AFSDGLAHLD NLKGTFATLS ELHCDKLHVD PENFRLLGNV LVCVLAHHFG
120 KEFTPPVQAA YQKVVAGVAN ALAHKYH
Hb Arta
1 VHLTPEEKS AVTALWGKVN VDEVGGEALG RPLVVYPWTQ RFFESCGDLS TPDAVMGNPK
60 VKAHGKKVLG AFSDGLAHLD NLKGTFATLS ELHCDKLHVD PENFRLLGNV LVCVLAHHFG
120 KEFTPPVQAA YQKVVAGVAN ALAHKYH
Hb S-Antilles
1 VHLTPVEKS AVTALWGKVN VDEIGGEALG RPLVVYPWTQ RFFESCGDLS TPDAVMGNPK
60 VKAHGKKVLG AFSDGLAHLD NLKGTFATLS ELHCDKLHVD PENFRLLGNV LVCVLAHHFG
120 KEFTPPVQAA YQKVVAGVAN ALAHKYH
Hb C-iquinchor
1 VHLTPVEKS AVTALWGKVN VDEVGGEALG RPLVVYPWTQ RFFESCGDLS TPDAVMGNRK
60 VKAHGKKVLG AFSDGLAHLD NLKGTFATLS ELHCDKLHVD PENFRLLGNV LVCVLAHHFG
120 KEFTPPVQAA YQKVVAGVAN ALAHKYH
Hb S-Pro!idence
1 VHLTPVEKS AVTALWGKVN VDEVGGEALG RPLVVYPWTQ RFFESCGDLS TPDAVMGNPK
60 VKAHGKKVLG AFSDGLAHLD NLDGTFATLS ELHCDKLHVD PENFRLLGNV LVCVLAHHFG
120 KEFTPPVQAA YQKVVAGVAN ALAHKYH
Hb S-"ra!is
1 VHLTPVEKS AVTALWGKVN VDEVGGEALG RPLVVYPWTQ RFFESCGDLS TPDAVMGNPK
60 VKAHGKKVLG AFSDGLAHLD NLKGTFATLS ELHCDKLHVD PENFRLLGNV LVCVLAHHFG
120 KEFTPPVQAA YQKVVAGVAN ALVHKYH
Hb #renoble
1 VHLTPEEKS AVTALWGKVN VDEVGGEALG RPLVVYPWTQ RFFESCGDLS TS$AVMGNPK
60 VKAHGKKVLG AFSDGLAHLD NLKGTFATLS ELHCDKLHVD PENFRLLGNV LVCVLAHHFG
120 KEFTPPVQAA YQKVVAGVAN ALAHKYH
Hb %odaira
1 VHLTPEEKS AVTALWGKVN VDEVGGEALG RPLVVYPWTQ RFFESCGDLS TPDAVMGNPK
60 VKAHGKKVLG AFSDGLAHLD NLKGTFATLS ELHCDKLHVD PENFRLLGNV LVCVLAHHFG
120 KEFTPPVQAA YQKVVAGVAN ALAHKY&
Hb S-'man
1 VHLTPVEKS AVTALWGKVN VDEVGGEALG RPLVVYPWTQ RFFESCGDLS TPDAVMGNPK
60 VKAHGKKVLG AFSDGLAHLD NLKGTFATLS ELHCDKLHVD PENFRLLGNV LVCVLAHHFG
120 K%FTPPVQAA YQKVVAGVAN ALAHKYH
Hb C-Harlem
1 VHLTPVEKS AVTALWGKVN VDEVGGEALG RPLVVYPWTQ RFFESCGDLS TPDAVMGNPK
60 VKAHGKKVLG AFS$GLAHLD NLKGTFATLS ELHCDKLHVD PENFRLLGNV LVCVLAHHFG
120 KEFTPPVQAA YQKVVAGVAN ALAHKYH
Hb (ien
1 VHLTPEEKS AVTALWGKVN VDEVGGEALG RPLVVYPWTQ RFFESCGDLS TPDAVMGNPK
60 VKAHGKKVLG AFSDGLAHLD NLKGTFATLS ELHCDKLHVD PENFRLLGNV LVCVLAHHFG
120 KEFTPPVQAA DQKVVAGVAN ALAHKYH
The following m%tated amino acid se0%ences have the predicted secondary str%ct%re
shown below#
CCCCHHHHHHHHHHHCCCCHHHHHHHHHHHHHEECHHHHHHHHHCCCCCCHHHHCCCCCH
HHCHHHHHHHHHHHHHHHHHHHHHHHHHHHHCCCCCCCCHHHHHHHHHHHHHHHHHHHCC
CCCHHHHHHHHHHHHHHHHHHHHHCC
This differs only slightly from the predicted secondary str%ct%re for the .BB se0%ence.
The do%ble %nderlined bold font ., in the above secondary str%ct%re, has a / predicted in
the e0%ivalent position in the .BB secondary str%ct%re prediction.
Hb %o)u
1 VHLTPEEKS AVTALWGKVN VDEVGGEALG RPLVVYPWTQ RFFESCGDLS TPDAVMGNPK
60 VKAHGKKVLG AFSDGLAHLD NLKGIFATLS ELHCDKLHVD PENFRLLGNV LVCVLAHHFG
120 KEFTPPVQAA YQKVVAGVAN ALAHKYH
Hb Yatsushiro
1 VHLTPEEKS AVTALWGKVN VDEVGGEALG RPLVVYPWTQ RFFESCGDLS TPDAVMGNPK
60 LKAHGKKVLG AFSDGLAHLD NLKGTFATLS ELHCDKLHVD PENFRLLGNV LVCVLAHHFG
120 KEFTPPVQAA YQKVVAGVAN ALAHKYH
Hb Poiss*
1 VHLTPEEKS AVTALWGKVN VDEVGGEALG RPLVVYPWTQ RFFESCGDLS TPDAVMRNPK
60 VKAHGKKVLG AFSDGLAHLD NLKGTFPTLS ELHCDKLHVD PENFRLLGNV LVCVLAHHFG
120 KEFTPPVQAA YQKVVAGVAN ALAHKYH
Hb "-Cambodia
1 VHLTPEEKS AVTALWGKVN VDEVGG%ALG RPLVVYPWTQ RFFESCGDLS TPDAVMGNPK
60 VKAHGKKVLG AFSDGLAHLD NLKGTFATLS ELHCDKLHVD PENFRLLGNV LVCVLAHHFG
120 K&FTPPVQAA YQKVVAGVAN ALAHKYH
Hb Arlington Park
1 VHLTP%EKS AVTALWGKVN VDEVGGEALG RPLVVYPWTQ RFFESCGDLS TPDAVMGNPK
60 VKAHGKKVLG AFSDGLAHLD NLKGTFATLS ELHCD+LHVD PENFRLLGNV LVCVLAHHFG
120 KEFTPPVQAA YQKVVAGVAN ALAHKYH
Hb D,el)a
1 VHLTPEEKS AVTALWGKVN VDEVGGEALG RPLVVYPWTQ RFFESCGDLS TPDAVMGNPK
60 VKAHGKKVLG AFSDGLAHLD NLKGTFATLS ELHCDKLHAD PENFRLLGNV LVCVLAHHFG
120 KEFTPPVQAA YQKVVAGVAN ALAHKYH
________________________________________________________________________
Step 6 : Protein 7ertiary Structure Pre%iction
'tep five involves predicting the tertiary str%ct%re of proteins that are prod%ced by the
normal and m%tated genes. The tertiary str%ct%res of .BB , .b ' and .b -rlington (ark
se0%ences are presented here. The amino acid se0%ences were fed into the C$% &odels
Ser"er (http#$$www.cbs.dt%.dk$services$/(.models$inde&.html). n addition to
prod%cing three dimensional protein str%ct%re images, this site also prod%ces a file of
atomic coordinates. These files were imported into the 4asHol vis%alization tool and
e&ported into a ;O image format, which were then imported into this doc%ment.
By vis%ally e&amining these images, it is diffic%lt to notice the str%ct%re
differences. To verify that the str%ct%res are different, %sed the H' 98' command 'C
to compare the atomic coordinate files. The O/ command takes two file names as
parameters and o%tp%ts the differences among the files. "sing this command, verified
that there were atomic coordinate differences among the files thereby proving that
str%ct%ral differences do indeed e&ists.
Pre%icte% +BB Structure
Pre%icte% Structure of +b S

Pre%icte% Structure of +b Arlington Park Structure
________________________________________________________________________
Step 8 : 92amine :nknown "ene Mutation an% (eulting Protein Structure
'tep 5 involved e&amining the protein str%ct%res that res%lt from %nknown gene
m%tations. created s%ch m%tations by randomly altering certain bases.
________________________________________________________________________
The following table details two %nknown m%tations
+b $ame (ei%e $umber Amino Aci% Subtitution "ene Mutation
H'mith1 1 Jal*IHet ;";*I-";
< (ro*I:e% //"*I///
23 Jal*IHet ;";*I-";
21 -sp*I;l% ;-"*I;-;
1?5 .is*IJal /-/*I/"/
H'mith2 5 ;l%*IJal ;-;*I;T;
133 (ro*I-la //"*I;/"
131 ;l%*I-la ;-;*I;/"
132 -sn*I'er --/*I-;/
Primary an% Pre%icte% Secon%ary Structure of MSmith1 (m%tated amino acids are in
bold font)
Pri. Sr!"!r# $ -HLTLEEKSAVTALWGKVN-+EVGGEALGRLLVVYPWTQRFFESFGDLSTPDAVMGNPKV
S#". Sr!"!r# $ CCCCHHHHHHHHHHHCCCCHHHHHHHHHHHHHEECHHHHHHHHHCCCCCCHCHHCCCCCH
Pri. Sr!"!r# $ KAHGKKVLGAFSDGLAHLDNLKGTFATLSELHCDKLHVDPENFRLLGNVLVCVLAHHFGK
S#". Sr!"!r# $ HHCHHHHHHHHHHHHHHHHHHHHHHHHHHHHCCCCCCCCHHHHHHHHHHHHHHHHHHHCC
Pri. Sr!"!r# $ EFTPPVQAAYQKVVAGVANALAHKYV
S#". Sr!"!r# $ CCCHHHHHHHHHHHHHHHHHHHHCCC
This differs from the predicted secondary str%ct%re for the .BB se0%ence in that the bold
font, do%ble %nderlined / is predicted to be an . in the secondary str%ct%re of the .BB
se0%ence
Pre%icte% 7ertiary Structure of MSmith1
Primary an% Pre%icte% Secon%ary Structure of MSmith! (m%tated amino acids are in
bold font)
Pri. Sr!"!r# $ VHLTPVEKSAVTALWGKVNVDEVGGEALGRLLVVYPWTQRFFESFGDLSTPDAVMGNPKV
S#". Sr!"!r# $ CCCCHHHHHHHHHHHCCCCHHHHHHHHHHHHHEECHHHHHHHHHCCCCCCHCHHCCCCCH
Pri. Sr!"!r# $ KAHGKKVLGAFSDGLAHLDNLKGTFATLSELHCDKLHVDAASFRLLGNVLVCVLAHHFGK
S#". Sr!"!r# $ HHCHHHHHHHHHHHHHHHHHHHHHHHHHHHHCCCCCCCCHHHHHHHHHHHHHHHHHHHCC
Pri. Sr!"!r# $ EFTPPVQAAYQKVVAGVANALAHKYH
S#". Sr!"!r# $ CCCHHHHHHHHHHHHHHHHHHHHHCC
This predicted secondary str%ct%re is the same as that of the predicted secondary str%ct%re
of the .BB se0%ence
Pre%icte% 7ertiary Structure of MSmith!