1n86

From Proteopedia

(Difference between revisions)

Revision as of 07:19, 7 February 2018

Crystal structure of human D-dimer from cross-linked fibrin complexed with GPR and GHRPLDK peptide ligands.

Structural highlights

1n86 is a 10 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, ,
Related:	1n73, 1fzc, 1n8e
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[FIBA_HUMAN] Defects in FGA are a cause of congenital afibrinogenemia (CAFBN) [MIM:202400]. This is a rare autosomal recessive disorder characterized by bleeding that varies from mild to severe and by complete absence or extremely low levels of plasma and platelet fibrinogen. Note=The majority of cases of afibrinogenemia are due to truncating mutations. Variations in position Arg-35 (the site of cleavage of fibrinopeptide a by thrombin) leads to alpha-dysfibrinogenemias. Defects in FGA are a cause of amyloidosis type 8 (AMYL8) [MIM:105200]; also known as systemic non-neuropathic amyloidosis or Ostertag-type amyloidosis. AMYL8 is a hereditary generalized amyloidosis due to deposition of apolipoprotein A1, fibrinogen and lysozyme amyloids. Viscera are particularly affected. There is no involvement of the nervous system. Clinical features include renal amyloidosis resulting in nephrotic syndrome, arterial hypertension, hepatosplenomegaly, cholestasis, petechial skin rash.^[1] [FIBB_HUMAN] Defects in FGB are a cause of congenital afibrinogenemia (CAFBN) [MIM:202400]. This rare autosomal recessive disorder is characterized by bleeding that varies from mild to severe and by complete absence or extremely low levels of plasma and platelet fibrinogen. Note=Patients with congenital fibrinogen abnormalities can manifest different clinical pictures. Some cases are clinically silent, some show a tendency toward bleeding and some show a predisposition for thrombosis with or without bleeding.

Function

[FIBA_HUMAN] Fibrinogen has a double function: yielding monomers that polymerize into fibrin and acting as a cofactor in platelet aggregation. [FIBB_HUMAN] Fibrinogen has a double function: yielding monomers that polymerize into fibrin and acting as a cofactor in platelet aggregation.

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

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 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^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Benson MD, Liepnieks J, Uemichi T, Wheeler G, Correa R. Hereditary renal amyloidosis associated with a mutant fibrinogen alpha-chain. Nat Genet. 1993 Mar;3(3):252-5. PMID:8097946 doi:http://dx.doi.org/10.1038/ng0393-252
↑ Yang Z, Pandi L, Doolittle RF. The crystal structure of fragment double-D from cross-linked lamprey fibrin reveals isopeptide linkages across an unexpected D-D interface. Biochemistry. 2002 Dec 31;41(52):15610-7. PMID:12501189

1 Structural highlights
2 Disease
3 Function
4 Evolutionary Conservation
5 Publication Abstract from PubMed
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1n86"

@@ Line 1: / Line 1: @@
 ==Crystal structure of human D-dimer from cross-linked fibrin complexed with GPR and GHRPLDK peptide ligands.==
 <StructureSection load='1n86' size='340' side='right' caption='[[1n86]], [[Resolution|resolution]] 3.20&Aring;' scene=''>
@@ Line 5: / Line 6: @@
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NDG:2-(ACETYLAMINO)-2-DEOXY-A-D-GLUCOPYRANOSE'>NDG</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1n73|1n73]], [[1fzc|1fzc]], [[1n8e|1n8e]]</td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1n86 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1n86 OCA], [http://pdbe.org/1n86 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1n86 RCSB], [http://www.ebi.ac.uk/pdbsum/1n86 PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1n86 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1n86 OCA], [http://pdbe.org/1n86 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1n86 RCSB], [http://www.ebi.ac.uk/pdbsum/1n86 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1n86 ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 15: / Line 16: @@
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/n8/1n86_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/n8/1n86_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
@@ Line 30: / Line 31: @@
 </div>
 <div class="pdbe-citations 1n86" style="background-color:#fffaf0;"></div>
-==See Also==
-*[[Fibrin|Fibrin]]
-*[[Fibrinogen|Fibrinogen]]
 == References ==
 <references/>

1n86

From Proteopedia

Revision as of 07:19, 7 February 2018

Crystal structure of human D-dimer from cross-linked fibrin complexed with GPR and GHRPLDK peptide ligands.

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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