1mkw
From Proteopedia
(New page: 200px<br /><applet load="1mkw" size="450" color="white" frame="true" align="right" spinBox="true" caption="1mkw, resolution 2.3Å" /> '''THE CO-CRYSTAL STRUCT...) |
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| - | [[Image:1mkw.jpg|left|200px]]<br /><applet load="1mkw" size=" | + | [[Image:1mkw.jpg|left|200px]]<br /><applet load="1mkw" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1mkw, resolution 2.3Å" /> | caption="1mkw, resolution 2.3Å" /> | ||
'''THE CO-CRYSTAL STRUCTURE OF UNLIGANDED BOVINE ALPHA-THROMBIN AND PRETHROMBIN-2: MOVEMENT OF THE YPPW SEGMENT AND ACTIVE SITE RESIDUES UPON LIGAND BINDING'''<br /> | '''THE CO-CRYSTAL STRUCTURE OF UNLIGANDED BOVINE ALPHA-THROMBIN AND PRETHROMBIN-2: MOVEMENT OF THE YPPW SEGMENT AND ACTIVE SITE RESIDUES UPON LIGAND BINDING'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Unliganded bovine alpha-thrombin and prethrombin-2 have been | + | Unliganded bovine alpha-thrombin and prethrombin-2 have been co-crystallized, in space group P21212, using either ammonium sulfate or polyethylene glycol 2000 (PEG2K), and their structures determined at 2.2 A and 2.3 A, respectively. Initial phases were determined by molecular replacement and refined using XPLOR to final R factors of 0.187 (Rfree = 0.255) and 0.190 (Rfree = 0.282) for the salt and PEG2K models, respectively. The apo-enzyme form of bovine alpha-thrombin shows dramatic shifts in placement for the Tyr-Pro-Pro-Trp segment, for Glu-192, and for the catalytic residues His-57 and Ser-195, when compared to 4 thrombin complexes representing different states of catalysis, namely (1) the Michaelis complex (residues 7-19 of fibrinogen A alpha with a non-cleavable scissile bond), (2) enzyme-inhibitor complex (D-Phe-Pro-Arg chloromethylketone), (3) enzyme product complex (residues 7-16 of fibrinopeptide A), and (4) the exosite complex (residues 53-64 of hirudin). The structures of bovine and human prethrombin-2 are generally similar to one another (RMS deviation of 0.68 A) but differ significantly in the Arg-15/Ile-16 cleavage region and in the three activation domains, which are disordered in bovine prethrombin-2, analogous to that seen for trypsinogen. |
==About this Structure== | ==About this Structure== | ||
| - | 1MKW is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus]. Active as [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] Full crystallographic information is available from [http:// | + | 1MKW is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus]. Active as [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] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1MKW OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Protein complex]] | [[Category: Protein complex]] | ||
[[Category: Thrombin]] | [[Category: Thrombin]] | ||
| - | [[Category: Edwards, B | + | [[Category: Edwards, B F.P.]] |
| - | [[Category: Malkowski, M | + | [[Category: Malkowski, M G.]] |
[[Category: complex (blood coagulation/proenzyme)]] | [[Category: complex (blood coagulation/proenzyme)]] | ||
[[Category: plasma]] | [[Category: plasma]] | ||
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[[Category: thrombin]] | [[Category: thrombin]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:56:15 2008'' |
Revision as of 11:56, 21 February 2008
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THE CO-CRYSTAL STRUCTURE OF UNLIGANDED BOVINE ALPHA-THROMBIN AND PRETHROMBIN-2: MOVEMENT OF THE YPPW SEGMENT AND ACTIVE SITE RESIDUES UPON LIGAND BINDING
Overview
Unliganded bovine alpha-thrombin and prethrombin-2 have been co-crystallized, in space group P21212, using either ammonium sulfate or polyethylene glycol 2000 (PEG2K), and their structures determined at 2.2 A and 2.3 A, respectively. Initial phases were determined by molecular replacement and refined using XPLOR to final R factors of 0.187 (Rfree = 0.255) and 0.190 (Rfree = 0.282) for the salt and PEG2K models, respectively. The apo-enzyme form of bovine alpha-thrombin shows dramatic shifts in placement for the Tyr-Pro-Pro-Trp segment, for Glu-192, and for the catalytic residues His-57 and Ser-195, when compared to 4 thrombin complexes representing different states of catalysis, namely (1) the Michaelis complex (residues 7-19 of fibrinogen A alpha with a non-cleavable scissile bond), (2) enzyme-inhibitor complex (D-Phe-Pro-Arg chloromethylketone), (3) enzyme product complex (residues 7-16 of fibrinopeptide A), and (4) the exosite complex (residues 53-64 of hirudin). The structures of bovine and human prethrombin-2 are generally similar to one another (RMS deviation of 0.68 A) but differ significantly in the Arg-15/Ile-16 cleavage region and in the three activation domains, which are disordered in bovine prethrombin-2, analogous to that seen for trypsinogen.
About this Structure
1MKW is a Protein complex structure of sequences from Bos taurus. Active as Thrombin, with EC number 3.4.21.5 Full crystallographic information is available from OCA.
Reference
The co-crystal structure of unliganded bovine alpha-thrombin and prethrombin-2: movement of the Tyr-Pro-Pro-Trp segment and active site residues upon ligand binding., Malkowski MG, Martin PD, Guzik JC, Edwards BF, Protein Sci. 1997 Jul;6(7):1438-48. PMID:9232645
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