Eahc Tesis

Estudios de estructura y función de las

interacciones de la trombina con
sustratos fisiológicos
Erick Adolfo Hernández Carvajal

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HG3(<P)3&<PH3)
@ (AHP &3' +&(&(&( AAA
:,';:,';:,';
,'3,<,N3G<(HI3H
@ (A, )3, #&&&( AAA
:,';:,';:,';
-# ! ,B#!C! ,- 1,9- C !(
HH3I<N)3,<PI3I
@ (A(& (3N +&( AAA
:,';:,)%(;:,';
IG3H<NI3'<(&H3&
)3& +&(&(&(
9 @(A)' :,';:,';:,';

-# ! ,B#!C! ,- 1,9- C !( &7A<*
II3(<(HI3H<IP3'
:,';:,H3&;:,';
@ (A&G &3&, +&(
v
3
G(3G<NN3N<P)3H
@ &A)& (3NG +&(&(&(
:,';:,';:,';
&H,
- .6
,(3)<,N3H<(HG3P
@ &A&G )3& #&&&(
:,';:,';:,';

-# ! ,B#!C! ,- 1,9- C &
HH3H<N)3,<PG3,
@ (AH (3, +&(
:,';:,&3P;:,';
HH3)<NH3'HPI3(
@ (A(I &3I +&(
:,';:,)3H&;:,';
HH3N<NH3P<PI3N
@ &AH' (3, +&(
:,';:,)3),;:,';
(&H3I<HN3P<G'3,
+ A+8(A), &3' #&
:,';:,G3';:,';
(&H3G<HN3P<G&3&
+ A+8(AHI )3( #&
:,';:,G3P;:,';
HH3&<NH3'<PI3'
@ (AP (3I +&(&(&(
:,';:,';:,';
HH3I<NG3(<PN3)
@ (AH' &3( +&(&(&(
:,';:,';:,';

-# ! ,B#!C! ,- 1,9- C & '*
&G'
- .6
HH3G<NH3I<PI3&
@ (AH &3) +&(&(&(
:,';:,';:,';

-# ! ,B#!C! ,- 1,9- C & '*? (
II3&<(HG3,<IP3IN
@ (A&G &3I +&( AAA
:,';:,H3P&;:,';
II3I<(HG3P<II3N
@ (A&, &3) +&(
:,';:,)3,;:,';
HH3,<NI3(<PI3I
@ (A(& )3( +&(&(&(
:,';:,'3(I;:,';
G&3(<NN3P<P)3G
@ (A&H (3N +&(&(&(
:,';:,';:,';
,(3'<,P3&<(HG3,
@ (A&( )3G #&&&(
:,';:,';:,';
,(3'<,N3,<(HI3(
@ (A&G )3& #&&&(
:,';:,';:,';
,(3&<,P3'<(HG3'
@ &A&G )3' #&&&( :,';:P,3G;:,';

&G(

- ..
1- && 9- ! ,!9 C "-9 ,!#- -9 P 5 Q !9$ !C-9 ! "-9 9CB-9 C" !&
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5 4 U%J%U. J.
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&GH
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&GG
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&GP
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*C000 (3K . . 4
4 9 5 : 9 ; "
('-('-&'(&:===34 43= 3 ;3K J . %
( *C000@ 3
9CB- D- 9D"!H! - 9CB- D- 9D"!H! -
C" !& C G-- OBL,- C" !& C G-- OBL,-
E11 # H,3)HG ))I N3,,N
E11 # (I3(I) ))I L (&(3(')
&E1E P3H,' ))I # G&3PP,
&E1E L ((G3)&& ))I # &N3I((
&E1E # GG3''( ))I # (NG3,G,
&E1E # I'3P&) ))N P3(,'
&E1E # (N)3PGG ))N L (&(3&&&
; E1 P3G() ))N # G&3HGI
; E1 L (&'3)&G ))N # &,3N()
; E1 # G&3',N ))N # (NI3'HN
; E1 # &I3)(( K ))P P3(PG
+ ))' L ()I3G'( K ))P L (&&3&G)
+ ))' # I'3I), K ))P # G)3H&G
+ ))' # &P3,GI K ))P # &,3,NI
+ ))' # (NN3'(' K ))P # (NI3'I&
E))( P3),I )), P3)N&
E))( L ((,3G&& )), L ((,3G'N
E))( # G&3,&N )), # G'3&'&
E))( # &I3'G) )), # )G3I(,
+ ))) L ()I3N,H )), # (NH3PHG
+ ))) # I'3GP' )H' P3&GI
+ ))) # &,3'H, )H' L ((P3&&(
+ ))) # (NI3HG' )H' # G'3G&N
E))H P3II) )H' # )G3HHN
E))H L (&'3'(G )H' # (NG3'N)
E))H # G)3I&) E)H( P3(PH
E))H # &I3G), E)H( L ((,3PNP
E))H # (NG3,') E)H( # G)3N,P
K))G N3,I) E)H( # &I3PI,
K))G L (&&3GPP )H) P3'GH
K))G # ),3(HI )H) L (&H3GN)
K))G # G&3&,, )H) # H,3H'I
K))G # (NI3,,) )H) # (I3)P&
&G,
- .1
9CB- D- 9D"!H! - 9CB- D- 9D"!H! -
C" !& C G-- OBL,- C" !& C G-- OBL,-
)H) # (NN3HNG )G& # )N3PN(
E)HH P3(GI )G& # (NI3)H)
E)HH L ((,3NG) / )G) P3(''
E)HH # &N3(,& / )G) L ((I3('P
E)HH # G)3&NH / )G) # GG3PPN
E)HH # (NG3I)) / )G) # I'3N)P
)HG P3'I( / )G) # (NH3P(&
)HG L (&'3G(G E)GH P3&'P
)HG # G(3&GI E)GH L (&&3(NG
)HG # )N3,PI E)GH # G)3N'H
)HG # (NG3GG, E)GH # &I3NP)
)HI N3PII E)GH # (NI3HPP
)HI L (&'3&(H )GG N3,IG
)HI # GH3I'' )GG L ((,3NPG
)HI # )I3'HG )GG # G&3G&G
)HI # (NG3()G )GG # &,3N()
)HN P3(H) )GG # (NG3PHP
)HN L (&(3N)' )GI P3'PP
)HN # G'3,HN )GI L (&(3(NH
)HN # )P3&)N )GI # G(3&II
)HN # (NG3G&I )GI # )N3PPH
)HP P3'II )GI # (NG3,G,
)HP L (&'3,'H C )GN N3NH)
)HP # )P3('G C )GN L (&'3'GG
)HP # G)3))( C )GN # G,3&&(
)HP # (NG3)HI C )GN # &,3N&H
)H, N3,,' C )GN # (NG3P'P
)H, L (&'3&HG C )GP P3'''
)H, # G(3&I' C )GP L (&H3,N'
)H, # )P3'(P C )GP # G,3H''
)H, # (NI3(,P C )GP # &,3)I'
K)G' P3'&& C )GP # (NG3HN(
K)G' L (&(3,HG )G, P3(&&
K)G' # G&3'PG )G, L (&G3),,
K)G' # )P3,(N )G, # G&3)(I
K)G' # (NN3INH )G, # &P3)(I
@ )G( N3,PP )G, # (NG3G'&
@ )G( L ((H3)HI +@)I' P3&G&
@ )G( # G,3(NG +@)I' L (&(3,NI
@ )G( # II3P'( +@)I' # GH3HNN
@ )G( # (NH3),& +@)I' # )I3N&)
)G& P3&() +@)I' # (NG3&GI
)G& L (&&3H'G )I( P3(P)
)G& # G(3GP( )I( L (&(3GHP
&I'
- .1
9CB- D- 9D"!H! - 9CB- D- 9D"!H! -
C" !& C G-- OBL,- C" !& C G-- OBL,-
)I( # G(3'(I E)N' P3('N
)I( # )P3'(( E)N' L (&H3G,N
)I( # (NG3NGP E)N' # G&3N')
)I& P3(IG E)N' # &I3)I(
)I& L ((,3,HP E)N' # (NG3IP)
)I& # G(3&(N 0)N( P3(()
)I& # )N3,&' 0)N( L (&)3G'(
)I& # (NG3IN& 0)N( # GP3(&,
)I) P3'IG 0)N( # )G3)G&
)I) L (&'3)(N 0)N( # (NI3&'N
)I) # )N3P'& )N& P3)',
)I) # G(3HNH )N& L (&G3NN&
)I) # (NG3,&& )N& # G)3(I,
)IH P3(', )N& # &N3NP&
)IH L ((P3&PH )N& # (NI3I'P
)IH # G'3'&P 9"ENE P3&NN
)IH # )G3PI( 9"ENE L (('3G((
)IH # (NH3P,' 9"ENE # H&3(''
/ )IG N3,G& 9"ENE # (N)3,)&
/ )IG L ((N3',) &EN P3(PP
/ )IG # G)3PGI &EN L ((G3G&(
/ )IG # I'3(HI &EN # I'3P&&
/ )IG # (N&3NII &EN # GG3GIP
+ )II L ()N3,,& &EN # (NG3((N
+ )II # I'3HIN 9"EN8 P3)N,
+ )II # &P3,IG 9"EN8 L (((3(NN
+ )II # (NI3PG' 9"EN8 # H&3&H,
/ )IN P3',( 9"EN8 # (N)3&(P
/ )IN L ((G3'G& " ENM N3II(
/ )IN # GG3),( " ENM L (&&3GHP
/ )IN # I'3I(P " ENM # GI3H'(
/ )IN # (NH3'NI " ENM # &I3'',
+@)IP N3,'& " ENM # (NP3IG(
+@)IP L (&&3(')
+@)IP # GG3'H,
+@)IP # )I3H,P
+@)IP # (NG3&P'
0)I, N3N)(
0)I, L (&)3'(N
0)I, # GN3,)G
0)I, # )G3IHN
0)I, # (NG3G''
&I(

- .E
1- &( !"-9 C "-9 C9D"!H! -9 OBL,-9 -#9.!C-9 C "-9 9CB-9
!9$ !C-9 C" E!$ - !& D9 ,! C -# !
/ " ! %L%#U%#J#

*C000 ( &'b 4 4 3K
. . 4 4 9
:===34 43= 3 ;3 K J . %
( *C000@ 3
9CB- D- 9D"!H! - 9CB- D- 9D"!H! -

C" !& C G-- OBL,- C" !& C G-- OBL,-
&E1E P3GNG K))G # (NI3())
&E1E L ((G3H,' ))I N3P(H
&E1E # I)3H&& ))I L (&I3,'(
&E1E # GN3PG, ))I # GI3P,P
&E1E # (N)3PN) ))I # )(3)&&
; E1 P3GG) K ))P P3IPP
; E1 L (&'3I(H K ))P L (&H3&&&
; E1 # GH3,)& K ))P # GI3()G
; E1 # &,3(IG K ))P # )&3PH'
+ ))' L ()I3,'I K ))P # (NG3N(N
+ ))' # I)3(G' )), P3I()
+ ))' # )(3,(N )), L (&'3NHN
+ ))' # (NI3G(( )), # G)3'(I
E))( P3I)& )), # )P3HG,
E))( L (&(3'NG )), # (NH3P(G
E))( # GI3'PN )H' P3)PH
E))( # &,3NG& )H' L ((P3IN(
E))( # (NI3()P )H' # G)3)GG
E))& P3&P) )H' # )P3)HG
E))& L (&)3GG& )H' # (NG3',N
E))& # GH3(N' E)H( P3)''
E))& # &,3)&P E)H( L (&'3'&&
+ ))) L ()N3()P E)H( # GI3I&(
+ ))) # I&3,G& E)H( # &,3G,,
+ ))) # )(3,(N E)H( # (NI3)')
+ ))) # (NI3GI' E)H& P3(((
E))H P3HG& E)H& L (&'3)''
E))H L (&'3P&I E)H& # GI3'PH
E))H # GG3(&, E)H& # &,3P&I
E))H # &,3((H E)H& # (NG3,&'
E))H # (NG3ING )H) P3'P(
K))G P3&GG )H) L (&H3)P)
K))G L (&H3G,G )H) # G&3',I
K))G # H(3PN( )H) # (,3())
K))G # GH3,&( )H) # (NN3HNH
&I)
- .E
9CB- D- 9D"!H! - 9CB- D- 9D"!H! -
C" !& C G-- OBL,- C" !& C G-- OBL,-
E)HH P3&H& / )G) # (NH3NP'
E)HH L ((,3P'( E)GH P3&,H
E)HH # &,3P,, E)GH L (&&3&'G
E)HH # GI3('' E)GH # GI3H'H
E)HH # (NG3IPI ' ()*+ ,- ./0*1*
)HG P3(HN ' ()*+ , 2310+/2
)HG L (&'3IH, )GG P3'HH
)HG # G)3I() )GG L (&'3''(
)HG # H'3N&) )GG # )&3G,'
)HG # (NG3)NH )GG # GG3)&)
)HI N3,)( )GG # (NG3PI&
)HI L (&'3HN, )GI P3(N)
)HI # GN3HH, )GI L (&(3)I&
)HI # )P3I)& )GI # GH3&&(
)HI # (NG3(I' )GI # H'3H,I
)HN P3(GN )GI # (NG3NPI
)HN L (&&3&IN C )GN N3P&H
)HN # G)3INH C )GN L (&'3&)G
)HN # H'3PNP C )GN # I&3('(
)HN # (NG3GNG C )GN # )&3G))
)HP P3'N) C )GN # (NG3PGN
)HP L (&'3)PH C )GP P3'PH
)HP # GH3(&H C )GP L (&G3'PG
)HP # H'3PH& C )GP # )&3(PG
)HP # (NI3''( C )GP # I&3(G&
)H, P3(G, C )GP # (NG3G''
)H, L (&'3)H) )G, P3(PP
)H, # H'3I', )G, L (&G3H)'
)H, # GH3)G' )G, # )(3'I&
)H, # (NI3&'P )G, # GG3((I
K)G' P3'PH )G, # (NG3G'I
K)G' L (&&3(P& +@)I' P3)'P
K)G' # GH3PP& +@)I' L (&(3,,'
K)G' # H(3I)& +@)I' # GN3)(G
K)G' # (NN3IPH +@)I' # ),3GIG
@ )G( P3'GH +@)I' # (NG3&&'
@ )G( L ((H3PI, )I( P3&G)
@ )G( # I&3(HG )I( L (&(3IGG
@ )G( # I,3G&P )I( # G)3NPG
@ )G( # (NH3)N, )I( # H'3P&&
)G& P3)'& )I( # (NG3HPI
)G& L (&&3GIG )I& P3'PH
)G& # GH3&N, )I& L (&(3&NN
)G& # H'3I(, )I& # GH3(',
)G& # (NI3)HH )I& # H'3PGH
/ )G) P3(N& )I& # (NG3N&'
/ )G) L ((I3)PI )I) P3&&(
/ )G) # GP3IPN )I) L (&'3(NI
/ )G) # I)3)PP )I) # H'3GPG
&IH
- .E
9CB- D- 9D"!H! - 9CB- D- 9D"!H! -
C" !& C G-- OBL,- C" !& C G-- OBL,-
)I) # GH3(&I 0)I, N3N,N
)I) # (NG3,GH 0)I, L (&)3HI&
)IH P3(P& 0)I, # I'3PIP
)IH L ((P3H(& 0)I, # )P3)&N
)IH # )P3I(I 0)I, # (NG3&',
)IH # G&3PNI E)N' N3,('
45)1+ , 23+0616 E)N' L ()'3N&&
7)1* 8 609./ E)N' # GN3'GH
/ )IG L ((N3(PI E)N' # )(3)(G
/ )IG # I&3PP' &EN P3IN&
/ )IG # GI3GI, &EN L ((G3I'G
+ )II L ()P3'&) &EN # I)3H((
+ )II # I&3HHP &EN # GP3(&N
+ )II # )(3P() &EN # (NH3NH&
+ )II # (NI3NN) 9"EN8 P3G'I
/ )IN P3(IH 9"EN8 L (((3H()
/ )IN L ((G3&)H 9"EN8 # HH3,',
/ )IN # GN3,)) 9"EN8 # (N)3(',
/ )IN # I)3),G " ENM N3NPI
/ )IN # (N)3,GN " ENM L (&&3GNG
+@)IP N3,PN " ENM # G,3',H
+@)IP L (&&3(NI " ENM # &P3N&G
+@)IP # GN3H&'
+@)IP # ),3)I)
+@)IP # (NG3'GG
&IG

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