2H43

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

Summary for 2H43

• Entry DOI: 10.2210/pdb2h43/pdb
• Related: 1FZG
• Descriptor: Fibrinogen alpha chain, Fibrinogen beta chain, Fibrinogen gamma chain, ... (7 entities in total)
• Functional Keywords: knob-hole interaction, fragment d, coiled-coil, blood clotting
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 8
• Total formula weight: 171051.43

Authors

Doolittle, R.F.,Pandi, L. (deposition date: 2006-05-23, release date: 2006-12-05, Last modification date: 2024-10-30)

Primary citation

Doolittle, R.F.,Chen, A.,Pandi, L.
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.
Biochemistry, 45:13962-13969, 2006

PubMed Abstract: 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.

PubMed: 17115691
DOI: 10.1021/bi061219e

Experimental method

X-RAY DIFFRACTION (2.7 Å)