1n8e
From Proteopedia
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|ACTIVITY= | |ACTIVITY= | ||
|GENE= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY=[[1fzc|1FZC]], [[1n86|1N86]], [[1n73|1N73]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1n8e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1n8e OCA], [http://www.ebi.ac.uk/pdbsum/1n8e PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1n8e RCSB]</span> | ||
}} | }} | ||
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==Overview== | ==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. | 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:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=134820 134820]], Afibrinogenemia, congenital OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=134830 134830]], Amyloidosis, hereditary renal OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=134820 134820]], Dysfibrinogenemia, alpha type, causing bleeding diathesis OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=134820 134820]], Dysfibrinogenemia, alpha type, causing recurrent thrombosis OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=134820 134820]], Dysfibrinogenemia, beta type OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=134830 134830]], Dysfibrinogenemia, gamma type OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=134850 134850]], Hypofibrinogenemia, gamma type OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=134850 134850]], Thrombophilia, dysfibrinogenemic OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=134830 134830]], Thrombophilia, dysfibrinogenemic OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=134850 134850]] | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: Yang, Z.]] | [[Category: Yang, Z.]] | ||
[[Category: cross-linked fibrin]] | [[Category: cross-linked fibrin]] | ||
| - | [[Category: d:d | + | [[Category: crystal packing]] |
| + | [[Category: d:d interface]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 22:26:52 2008'' |
Revision as of 19:26, 30 March 2008
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| , resolution 4.5Å | |||||||
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| Related: | 1FZC, 1N86, 1N73
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| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Fragment Double-D from Human Fibrin
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.
About this Structure
1N8E is a Protein complex structure of sequences from Homo sapiens. 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 Sun Mar 30 22:26:52 2008
