2a45: Difference between revisions
From Proteopedia
Jump to navigationJump to search
No edit summary |
No edit summary |
||
| Line 4: | Line 4: | ||
|PDB= 2a45 |SIZE=350|CAPTION= <scene name='initialview01'>2a45</scene>, resolution 3.65Å | |PDB= 2a45 |SIZE=350|CAPTION= <scene name='initialview01'>2a45</scene>, resolution 3.65Å | ||
|SITE= | |SITE= | ||
|LIGAND= <scene name='pdbligand=PO4:PHOSPHATE ION'>PO4</scene> | |LIGAND= <scene name='pdbligand=ARM:DEOXY-METHYL-ARGININE'>ARM</scene>, <scene name='pdbligand=DPN:D-PHENYLALANINE'>DPN</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene> | ||
|ACTIVITY= [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] | |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> | ||
|GENE= | |GENE= | ||
|DOMAIN= | |||
|RELATEDENTRY= | |||
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2a45 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2a45 OCA], [http://www.ebi.ac.uk/pdbsum/2a45 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2a45 RCSB]</span> | |||
}} | }} | ||
| Line 14: | Line 17: | ||
==Overview== | ==Overview== | ||
Nonsubstrate interaction of thrombin with fibrinogen promotes sequential cleavage of fibrinopeptides A and B (fpA and fpB, respectively) from the latter, resulting in its conversion into fibrin. The recently established crystal structure of human thrombin in complex with the central part of human fibrin clarified the mechanism of this interaction. Here, we reveal new details of the structure and present the results of molecular modeling of the fpA- and fpB-containing portions of the Aalpha and Bbeta chains, not identified in the complex, in both fibrinogen and protofibrils. The analysis of the results reveals that in fibrinogen the fpA-containing portions are in a more favorable position to bind in the active site cleft of bound thrombin. Surface plasmon resonance experiments establish that the fpB-containing portions interact with the fibrin-derived dimeric D-D fragment, suggesting that in protofibrils they bind to the newly formed DD regions bringing fpB into the vicinity of bound thrombin. These findings provide a coherent rationale for the preferential removal of fpA from fibrinogen at the first stage of fibrin assembly and the accelerated cleavage of fpB from protofibrils and/or fibrils at the second stage. | Nonsubstrate interaction of thrombin with fibrinogen promotes sequential cleavage of fibrinopeptides A and B (fpA and fpB, respectively) from the latter, resulting in its conversion into fibrin. The recently established crystal structure of human thrombin in complex with the central part of human fibrin clarified the mechanism of this interaction. Here, we reveal new details of the structure and present the results of molecular modeling of the fpA- and fpB-containing portions of the Aalpha and Bbeta chains, not identified in the complex, in both fibrinogen and protofibrils. The analysis of the results reveals that in fibrinogen the fpA-containing portions are in a more favorable position to bind in the active site cleft of bound thrombin. Surface plasmon resonance experiments establish that the fpB-containing portions interact with the fibrin-derived dimeric D-D fragment, suggesting that in protofibrils they bind to the newly formed DD regions bringing fpB into the vicinity of bound thrombin. These findings provide a coherent rationale for the preferential removal of fpA from fibrinogen at the first stage of fibrin assembly and the accelerated cleavage of fpB from protofibrils and/or fibrils at the second stage. | ||
==About this Structure== | ==About this Structure== | ||
| Line 31: | Line 31: | ||
[[Category: Medved, L.]] | [[Category: Medved, L.]] | ||
[[Category: Pechik, I.]] | [[Category: Pechik, I.]] | ||
[[Category: coiled coil]] | [[Category: coiled coil]] | ||
[[Category: disulfide ring]] | [[Category: disulfide ring]] | ||
| Line 40: | Line 39: | ||
[[Category: thrombin-fibrin complex]] | [[Category: thrombin-fibrin complex]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 01:47:35 2008'' | ||
