1fph: Difference between revisions

Revision as of 16:36, 2 May 2008

THE INTERACTION OF THROMBIN WITH FIBRINOGEN: A STRUCTURAL BASIS FOR ITS SPECIFICITY

OverviewOverview

The structure of the ternary complex of human alpha-thrombin with a covalently bound analogue of fibrinopeptide A and a C-terminal hirudin peptide has been determined by X-ray diffraction methods at 0.25 nm resolution. Fibrinopeptide A folds in a compact manner, bringing together hydrophobic residues that slot into the apolar binding site of human alpha-thrombin. Fibrinogen residue Phe8 occupies the aryl-binding site of thrombin, adjacent to fibrinogen residues Leu9 and Val15 in the S2 subsite. The species diversity of fibrinopeptide A is analysed with respect to its conformation and its interaction with thrombin. The non-covalently attached peptide fragment hirudin(54-65) exhibits an identical conformation to that observed in the hirudin-thrombin complex. The occupancy of the secondary fibrinogen-recognition exosite by this peptide imposes restrictions on the manner of fibrinogen binding. The surface topology of the thrombin molecule indicates positions P1'-P3', differ from those of the canonical serine-proteinase inhibitors, suggesting a mechanical model for the switching of thrombin activity from fibrinogen cleavage to protein-C activation on thrombomodulin complex formation. The multiple interactions between thrombin and fibrinogen provide an explanation for the narrow specificity of thrombin. Structural grounds can be put forward for certain congenital clotting disorders.

About this StructureAbout this Structure

1FPH is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

ReferenceReference

The interaction of thrombin with fibrinogen. A structural basis for its specificity., Stubbs MT, Oschkinat H, Mayr I, Huber R, Angliker H, Stone SR, Bode W, Eur J Biochem. 1992 May 15;206(1):187-95. PMID:1587268 Page seeded by OCA on Fri May 2 16:36:37 2008

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

@@ Line 1: / Line 1: @@
 [[Image:1fph.jpg|left|200px]]
- {{Structure
+<!--
-|PDB= 1fph |SIZE=350|CAPTION= <scene name='initialview01'>1fph</scene>, resolution 2.5&Aring;
+The line below this paragraph, containing "STRUCTURE_1fph", creates the "Structure Box" on the page.
-|SITE=
+You may change the PDB parameter (which sets the PDB file loaded into the applet)
-|LIGAND= <scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=CH2:METHYLENE+GROUP'>CH2</scene>
+or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-|ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Thrombin Thrombin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.5 3.4.21.5] </span>
+or leave the SCENE parameter empty for the default display.
-|GENE=
+-->
-|DOMAIN=
+{{STRUCTURE_1fph|  PDB=1fph  |  SCENE=  }}
-|RELATEDENTRY=
-|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1fph FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1fph OCA], [http://www.ebi.ac.uk/pdbsum/1fph PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1fph RCSB]</span>
-}}
 '''THE INTERACTION OF THROMBIN WITH FIBRINOGEN: A STRUCTURAL BASIS FOR ITS SPECIFICITY'''
@@ Line 28: / Line 25: @@
 [[Category: Bode, W.]]
 [[Category: Stubbs, M T.]]
-[[Category: hydrolase(serine proteinase)]]
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May  2 16:36:37 2008''
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 20:27:37 2008''