2a45

From Proteopedia

---

Revision as of 18:39, 12 November 2007

proteopedia linkproteopedia link

spinqualitylabelsall models 2a45, resolution 3.65Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

Crystal structure of the complex between thrombin and the central "E" region of fibrin

Contents 1 Overview 2 Disease 3 About this Structure 4 Reference

Overview

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.

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], Dysprothrombinemia OMIM:[176930], Hyperprothrombinemia OMIM:[176930], Hypofibrinogenemia, gamma type OMIM:[134850], Hypoprothrombinemia OMIM:[176930], Thrombophilia, dysfibrinogenemic OMIM:[134830], Thrombophilia, dysfibrinogenemic OMIM:[134850]

About this Structure

2A45 is a Protein complex structure of sequences from Homo sapiens with PO4 as ligand. This structure superseeds the now removed PDB entry 1QVH. The following page contains interesting information on the relation of 2A45 with [Fibrin]. Active as Thrombin, with EC number 3.4.21.5 Full crystallographic information is available from 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:16533041

Page seeded by OCA on Mon Nov 12 20:46:11 2007