1a61
From Proteopedia
(New page: 200px<br /> <applet load="1a61" size="450" color="white" frame="true" align="right" spinBox="true" caption="1a61, resolution 2.2Å" /> '''THROMBIN COMPLEXED W...) |
|||
| Line 1: | Line 1: | ||
| - | [[Image:1a61.gif|left|200px]]<br /> | + | [[Image:1a61.gif|left|200px]]<br /><applet load="1a61" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1a61" size=" | + | |
caption="1a61, resolution 2.2Å" /> | caption="1a61, resolution 2.2Å" /> | ||
'''THROMBIN COMPLEXED WITH A BETA-MIMETIC THIAZOLE-CONTAINING INHIBITOR'''<br /> | '''THROMBIN COMPLEXED WITH A BETA-MIMETIC THIAZOLE-CONTAINING INHIBITOR'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The X-ray crystal structures of four beta-strand-templated active site | + | The X-ray crystal structures of four beta-strand-templated active site inhibitors of thrombin containing P1' groups have been determined and refined at about 2.1-A resolution to crystallographic R-values between 0.148 and 0.164. Two of the inhibitors have an alpha-ketoamide functionality at the scissile bond; the other two have a nonhydrolyzable electrophilic group at the P1' position. The binding of lysine is compared with that of arginine at the S1 specificity site, while that of D,L-phenylalanine enantiomorphs is compared in the S3 region of thrombin. Four different P1' moieties bind at the S1' subsite in three different ways. The binding constants vary between 2.0 microM and 70 pM. The bound structures are used to intercorrelate the various binding constants and also lead to insightful inferences concerning binding at the S1' site of thrombin. |
==Disease== | ==Disease== | ||
| Line 11: | Line 10: | ||
==About this Structure== | ==About this Structure== | ||
| - | 1A61 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with NA, BIC and LOM 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:// | + | 1A61 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=NA:'>NA</scene>, <scene name='pdbligand=BIC:'>BIC</scene> and <scene name='pdbligand=LOM:'>LOM</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=1A61 OCA]. |
==Reference== | ==Reference== | ||
| Line 18: | Line 17: | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
[[Category: Thrombin]] | [[Category: Thrombin]] | ||
| - | [[Category: Charles, R | + | [[Category: Charles, R St.]] |
[[Category: Kahn, M.]] | [[Category: Kahn, M.]] | ||
| - | [[Category: Matthews, J | + | [[Category: Matthews, J H.]] |
[[Category: Tulinsky, A.]] | [[Category: Tulinsky, A.]] | ||
[[Category: Zhang, E.]] | [[Category: Zhang, E.]] | ||
| Line 28: | Line 27: | ||
[[Category: complex (serine protease/inhibitor)]] | [[Category: complex (serine protease/inhibitor)]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 11:41:16 2008'' |
Revision as of 09:41, 21 February 2008
|
THROMBIN COMPLEXED WITH A BETA-MIMETIC THIAZOLE-CONTAINING INHIBITOR
Contents |
Overview
The X-ray crystal structures of four beta-strand-templated active site inhibitors of thrombin containing P1' groups have been determined and refined at about 2.1-A resolution to crystallographic R-values between 0.148 and 0.164. Two of the inhibitors have an alpha-ketoamide functionality at the scissile bond; the other two have a nonhydrolyzable electrophilic group at the P1' position. The binding of lysine is compared with that of arginine at the S1 specificity site, while that of D,L-phenylalanine enantiomorphs is compared in the S3 region of thrombin. Four different P1' moieties bind at the S1' subsite in three different ways. The binding constants vary between 2.0 microM and 70 pM. The bound structures are used to intercorrelate the various binding constants and also lead to insightful inferences concerning binding at the S1' site of thrombin.
Disease
Known diseases associated with this structure: Dysprothrombinemia OMIM:[176930], Hyperprothrombinemia OMIM:[176930], Hypoprothrombinemia OMIM:[176930]
About this Structure
1A61 is a Protein complex structure of sequences from Homo sapiens with , and as ligands. Active as Thrombin, with EC number 3.4.21.5 Full crystallographic information is available from OCA.
Reference
Bound structures of novel P3-P1' beta-strand mimetic inhibitors of thrombin., St Charles R, Matthews JH, Zhang E, Tulinsky A, J Med Chem. 1999 Apr 22;42(8):1376-83. PMID:10212123
Page seeded by OCA on Thu Feb 21 11:41:16 2008
