2h43

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spinqualitylabelsall models 2h43, resolution 2.7Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

Crystal Structure of Human Fragment D Complexed with Ala-His-Arg-Pro-amide

Contents 1 Overview 2 Disease 3 About this Structure 4 Reference

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 CA and NH2 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

Page seeded by OCA on Mon Nov 12 22:25:58 2007