1doj: Difference between revisions
New page: left|200px<br /> <applet load="1doj" size="450" color="white" frame="true" align="right" spinBox="true" caption="1doj, resolution 1.70Å" /> '''CRYSTAL STRUCTURE O... |
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[[Image:1doj.gif|left|200px]]<br /> | [[Image:1doj.gif|left|200px]]<br /><applet load="1doj" size="350" color="white" frame="true" align="right" spinBox="true" | ||
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caption="1doj, resolution 1.70Å" /> | caption="1doj, resolution 1.70Å" /> | ||
'''CRYSTAL STRUCTURE OF HUMAN ALPHA-THROMBIN*RWJ-51438 COMPLEX AT 1.7 A'''<br /> | '''CRYSTAL STRUCTURE OF HUMAN ALPHA-THROMBIN*RWJ-51438 COMPLEX AT 1.7 A'''<br /> | ||
==Overview== | ==Overview== | ||
The three-dimensional structure of the ternary complex consisting of human | The three-dimensional structure of the ternary complex consisting of human alpha-thrombin, hirugen and the active-site inhibitor RWJ-51438 has been determined at 1.7 A resolution. The crystals of the complex belong to the orthorhombic space group P2(1)2(1)2, with unit-cell parameters a = 62.98, b = 117.52, c = 47.99 A. The refined R and R(free) values are 0.196 and 0.232, respectively. The ketone carbonyl group of the inhibitor is covalently linked to the hydroxyl O atom of Ser195, forming a tetrahedral intermediate hemiketal structure; the benzothiazole ring N atom of RWJ-51438 forms a hydrogen bond with His57. Surprisingly, the carboxylate substituent on the benzothiazole group forms salt bridges with Lys60F NZ and the NZ of the symmetry-related residues Lys236 and Lys240, which introduces steric effects that perturb the 60A-60I insertion loop, especially at residues Trp60D and Phe60H. | ||
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
1DOJ is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with NAG and NA as [http://en.wikipedia.org/wiki/ligands ligands]. 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:// | 1DOJ is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=NAG:'>NAG</scene> and <scene name='pdbligand=NA:'>NA</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. 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=1DOJ OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: Carson, M.]] | [[Category: Carson, M.]] | ||
[[Category: Chattopadhyay, D.]] | [[Category: Chattopadhyay, D.]] | ||
[[Category: Costanzo, M | [[Category: Costanzo, M J.]] | ||
[[Category: DeLucas, L.]] | [[Category: DeLucas, L.]] | ||
[[Category: Maryanoff, B | [[Category: Maryanoff, B E.]] | ||
[[Category: Recacha, R.]] | [[Category: Recacha, R.]] | ||
[[Category: NA]] | [[Category: NA]] | ||
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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 12:18:45 2008'' | ||
Revision as of 13:18, 21 February 2008
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CRYSTAL STRUCTURE OF HUMAN ALPHA-THROMBIN*RWJ-51438 COMPLEX AT 1.7 A
OverviewOverview
The three-dimensional structure of the ternary complex consisting of human alpha-thrombin, hirugen and the active-site inhibitor RWJ-51438 has been determined at 1.7 A resolution. The crystals of the complex belong to the orthorhombic space group P2(1)2(1)2, with unit-cell parameters a = 62.98, b = 117.52, c = 47.99 A. The refined R and R(free) values are 0.196 and 0.232, respectively. The ketone carbonyl group of the inhibitor is covalently linked to the hydroxyl O atom of Ser195, forming a tetrahedral intermediate hemiketal structure; the benzothiazole ring N atom of RWJ-51438 forms a hydrogen bond with His57. Surprisingly, the carboxylate substituent on the benzothiazole group forms salt bridges with Lys60F NZ and the NZ of the symmetry-related residues Lys236 and Lys240, which introduces steric effects that perturb the 60A-60I insertion loop, especially at residues Trp60D and Phe60H.
DiseaseDisease
Known diseases associated with this structure: Dysprothrombinemia OMIM:[176930], Hyperprothrombinemia OMIM:[176930], Hypoprothrombinemia OMIM:[176930]
About this StructureAbout this Structure
1DOJ is a Single protein structure of sequence from Homo sapiens with and as ligands. Active as Thrombin, with EC number 3.4.21.5 Full crystallographic information is available from OCA.
ReferenceReference
Structure of human alpha-thrombin complexed with RWJ-51438 at 1.7 A: unusual perturbation of the 60A-60I insertion loop., Recacha R, Costanzo MJ, Maryanoff BE, Carson M, DeLucas L, Chattopadhyay D, Acta Crystallogr D Biol Crystallogr. 2000 Nov;56(Pt 11):1395-400. PMID:11053836
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