2a45: Difference between revisions

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-[[Image:2a45.gif|left|200px]]
+[[Image:2a45.png|left|200px]]
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-==Overview==
+{{ABSTRACT_16533041}}
-Nonsubstrate interaction of thrombin with fibrinogen promotes sequential cleavage of fibrinopeptides A and B (fpA and fpB, respectively) from the latter, resulting in its conversion into fibrin. The recently established crystal structure of human thrombin in complex with the central part of human fibrin clarified the mechanism of this interaction. Here, we reveal new details of the structure and present the results of molecular modeling of the fpA- and fpB-containing portions of the Aalpha and Bbeta chains, not identified in the complex, in both fibrinogen and protofibrils. The analysis of the results reveals that in fibrinogen the fpA-containing portions are in a more favorable position to bind in the active site cleft of bound thrombin. Surface plasmon resonance experiments establish that the fpB-containing portions interact with the fibrin-derived dimeric D-D fragment, suggesting that in protofibrils they bind to the newly formed DD regions bringing fpB into the vicinity of bound thrombin. These findings provide a coherent rationale for the preferential removal of fpA from fibrinogen at the first stage of fibrin assembly and the accelerated cleavage of fpB from protofibrils and/or fibrils at the second stage.
 ==About this Structure==
 A45 is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=1qvh 1qvh]. The following page contains interesting information on the relation of 2A45 with [[http://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/pdb83_1.html Fibrin]]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2A45 OCA].
-==Reference==
-Structural basis for sequential cleavage of fibrinopeptides upon fibrin assembly., Pechik I, Yakovlev S, Mosesson MW, Gilliland GL, Medved L, Biochemistry. 2006 Mar 21;45(11):3588-97. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/16533041 16533041]
 [[Category: Fibrin]]
 [[Category: Homo sapiens]]
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 [[Category: Thrombin]]
 [[Category: Thrombin-fibrin complex]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May  3 18:34:38 2008''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Jun 26 18:11:13 2008''