1n86
From Proteopedia
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Crystal structure of human D-dimer from cross-linked fibrin complexed with GPR and GHRPLDK peptide ligands.
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Overview
The crystal structure of fragment double-D from factor XIII-cross-linked, lamprey fibrin has been determined at 2.9 A resolution. The 180 kDa, covalent dimer was cocrystallized with the peptide Gly-His-Arg-Pro-amide, which in many fibrinogens, but not that of lamprey, corresponds to the, B-knob exposed by thrombin. The structure was determined by molecular, replacement, a recently determined structure of lamprey fragment D being, used as a search model. GHRPam was found in both the gamma- and beta-chain, holes. Unlike the situation with fragment D, the crystal packing of the, cross-linked double-D structure exhibits two different D-D interfaces, each gamma-chain facing gamma-chains on two other molecules. One of these, (interface I) involves the asymmetric interface observed in all other D, fragments and related structures. The other (interface II) encompasses a, completely different set of residues. The two abutments differ in that, interface I results in an "in line" arrangement of abutting molecules and, the interface II in a "zigzag" arrangement. So far as can be determined, (the electron density could only be traced on one side of the, cross-links), it is the gamma-chains of the newly observed zigzag units, (interface II) that are joined by the reciprocal, epsilon-amino-gamma-glutamyl cross-links. Auspiciously, the same novel D-D, interface was observed in two lower-resolution crystal structures of human, double-D preparations that had been crystallized under unusual, circumstances. These observations show that double-D structures are linked, in a way that is sufficiently flexible to accommodate different D-D, interfaces under different circumstances.
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], Thrombophilia, dysfibrinogenemic OMIM:[134830]
About this Structure
1N86 is a Protein complex structure of sequences from Homo sapiens with NDG, MAN and CA as ligands. Full crystallographic information is available from OCA.
Reference
The crystal structure of fragment double-D from cross-linked lamprey fibrin reveals isopeptide linkages across an unexpected D-D interface., Yang Z, Pandi L, Doolittle RF, Biochemistry. 2002 Dec 31;41(52):15610-7. PMID:12501189
Page seeded by OCA on Mon Nov 12 18:19:09 2007
