2z4e

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{{STRUCTURE_2z4e| PDB=2z4e | SCENE= }}
{{STRUCTURE_2z4e| PDB=2z4e | SCENE= }}
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'''Crystal Structure of D-Dimer from Human Fibrin Complexed with Gly-His-Arg-Pro-Tyr-amide'''
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===Crystal Structure of D-Dimer from Human Fibrin Complexed with Gly-His-Arg-Pro-Tyr-amide===
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==Overview==
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In a recent report, we showed that alanine can replace glycine at the amino terminus of synthetic B-knobs that bind to human fibrin(ogen). We now report a survey of 13 synthetic peptides with the general sequence XHRPYam, all tested with regard to their ability to delay fibrinolysis in an in vitro system activated by t-PA, the results being used as measures of binding affinity to the betaC hole. Unexpectedly, some large and bulky amino acids, including methionine and arginine, are effective binders. Amino acids that branch at the beta carbon (valine, isoleucine, and threonine) do not bind effectively. Crystal structures were determined for two of the peptides (GHRPYam and MHRPYam) complexed with fibrin fragment D-dimer; the modeling of various other side chains showed clashing in the cases of beta-carbon substituents. The two crystal structures also showed that the enhanced binding observed with pentapeptides with carboxyl-terminal tyrosine, compared with that of their tetrapeptide equivalents, is attributable to an interaction between the tyrosine side chain and a guanidino group of a nearby arginine (beta406). The equivalent position in gamma-chains of human fibrin(ogen) is occupied by a lysine (gamma338), but in chicken and lamprey fibrin(ogen), it is an arginine, just as occurs in beta chains. Accordingly, the peptides GPRPam and GPRPYam, which are surrogate A-knobs, were tested for their influence on fibrin polymerization with fibrinogen from lamprey and humans. In lampreys, GPRPYam is a significantly better inhibitor, but in humans, it is less effective than GPRPam, indicating that in the lamprey system the same tyrosine-arginine interaction can also occur in the gamma-chain setting.
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(as it appears on PubMed at http://www.pubmed.gov), where 17688324 is the PubMed ID number.
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{{ABSTRACT_PUBMED_17688324}}
==About this Structure==
==About this Structure==
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[[Category: Blood clotting]]
[[Category: Blood clotting]]
[[Category: Fibrin clot]]
[[Category: Fibrin clot]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 19:56:18 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Jul 27 18:02:27 2008''

Revision as of 15:02, 27 July 2008

Image:2z4e.png

Template:STRUCTURE 2z4e

Crystal Structure of D-Dimer from Human Fibrin Complexed with Gly-His-Arg-Pro-Tyr-amide

Template:ABSTRACT PUBMED 17688324

About this Structure

2Z4E is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Probing the beta-chain hole of fibrinogen with synthetic peptides that differ at their amino termini., Doolittle RF, Pandi L, Biochemistry. 2007 Sep 4;46(35):10033-8. Epub 2007 Aug 10. PMID:17688324

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