2h43
From Proteopedia
(New page: 200px<br /> <applet load="2h43" size="450" color="white" frame="true" align="right" spinBox="true" caption="2h43, resolution 2.7Å" /> '''Crystal Structure of...) |
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| - | [[Image:2h43.gif|left|200px]]<br /> | + | [[Image:2h43.gif|left|200px]]<br /><applet load="2h43" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="2h43" size=" | + | |
caption="2h43, resolution 2.7Å" /> | caption="2h43, resolution 2.7Å" /> | ||
'''Crystal Structure of Human Fragment D Complexed with Ala-His-Arg-Pro-amide'''<br /> | '''Crystal Structure of Human Fragment D Complexed with Ala-His-Arg-Pro-amide'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The beta-chain amino-terminal sequences of all known mammalian fibrins | + | The beta-chain amino-terminal sequences of all known mammalian fibrins begin with the sequence Gly-His-Arg-Pro- (GHRP-), but the homologous sequence in chicken fibrin begins with the sequence Ala-His-Arg-Pro- (AHRP-). Nonetheless, chicken fibrinogen binds the synthetic peptide GHRPam, and a previously reported crystal structure has revealed that the binding is in exact conformance with that observed for the human GHRPam-fragment D complex. We now report that human fibrinogen, which is known not to bind APRP, binds the synthetic peptide AHRPam. Moreover, a crystal structure of AHRPam complexed with fragment D from human fibrinogen shows that AHRPam binds exclusively to the beta-chain hole and, unlike GHRPam, not at all to the homologous gamma-chain hole. The difference can be attributed to the methyl group of the alanine residue clashing with a critical carboxyl group in the gammaC hole but being accommodated in the roomier betaC hole where the equivalent carboxyl is situated more flexibly. |
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 2H43 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with CA and NH2 as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | + | 2H43 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=CA:'>CA</scene> and <scene name='pdbligand=NH2:'>NH2</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2H43 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
| - | [[Category: Doolittle, R | + | [[Category: Doolittle, R F.]] |
[[Category: Pandi, L.]] | [[Category: Pandi, L.]] | ||
[[Category: CA]] | [[Category: CA]] | ||
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[[Category: knob-hole interaction]] | [[Category: knob-hole interaction]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:38:00 2008'' |
Revision as of 15:38, 21 February 2008
|
Crystal Structure of Human Fragment D Complexed with Ala-His-Arg-Pro-amide
Contents |
Overview
The beta-chain amino-terminal sequences of all known mammalian fibrins begin with the sequence Gly-His-Arg-Pro- (GHRP-), but the homologous sequence in chicken fibrin begins with the sequence Ala-His-Arg-Pro- (AHRP-). Nonetheless, chicken fibrinogen binds the synthetic peptide GHRPam, and a previously reported crystal structure has revealed that the binding is in exact conformance with that observed for the human GHRPam-fragment D complex. We now report that human fibrinogen, which is known not to bind APRP, binds the synthetic peptide AHRPam. Moreover, a crystal structure of AHRPam complexed with fragment D from human fibrinogen shows that AHRPam binds exclusively to the beta-chain hole and, unlike GHRPam, not at all to the homologous gamma-chain hole. The difference can be attributed to the methyl group of the alanine residue clashing with a critical carboxyl group in the gammaC hole but being accommodated in the roomier betaC hole where the equivalent carboxyl is situated more flexibly.
Disease
Known diseases associated with this structure: Afibrinogenemia, congenital OMIM:[134820], Afibrinogenemia, congenital OMIM:[134830], Amyloidosis, hereditary renal OMIM:[134820], Dysfibrinogenemia, alpha type, causing bleeding diathesis OMIM:[134820], Dysfibrinogenemia, alpha type, causing recurrent thrombosis OMIM:[134820], Dysfibrinogenemia, beta type OMIM:[134830], Dysfibrinogenemia, gamma type OMIM:[134850], Hypofibrinogenemia, gamma type OMIM:[134850], Thrombophilia, dysfibrinogenemic OMIM:[134830], Thrombophilia, dysfibrinogenemic OMIM:[134850]
About this Structure
2H43 is a Protein complex structure of sequences from Homo sapiens with and as ligands. Full crystallographic information is available from OCA.
Reference
Differences in binding specificity for the homologous gamma- and beta-chain "holes" on fibrinogen: exclusive binding of Ala-His-Arg-Pro-amide by the beta-chain hole., Doolittle RF, Chen A, Pandi L, Biochemistry. 2006 Nov 28;45(47):13962-9. PMID:17115691
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