1lhd
From Proteopedia
(New page: 200px<br /> <applet load="1lhd" size="450" color="white" frame="true" align="right" spinBox="true" caption="1lhd, resolution 2.35Å" /> '''HUMAN ALPHA-THROMBI...) |
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caption="1lhd, resolution 2.35Å" /> | caption="1lhd, resolution 2.35Å" /> | ||
'''HUMAN ALPHA-THROMBIN COMPLEXED WITH AC-(D)PHE-PRO-BOROLYS-OH'''<br /> | '''HUMAN ALPHA-THROMBIN COMPLEXED WITH AC-(D)PHE-PRO-BOROLYS-OH'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The X-ray crystallographic structure of Ac-(D)Phe-Pro-boroArg-OH [DuP714, Ki = 0.04 nM; Kettner, C., Mersinger, L., & Knabb, R. (1990) J. Biol. | + | The X-ray crystallographic structure of Ac-(D)Phe-Pro-boroArg-OH [DuP714, Ki = 0.04 nM; Kettner, C., Mersinger, L., & Knabb, R. (1990) J. Biol. Chem. 265, 18289] complexed with human alpha-thrombin shows the boron atom covalently bonded to the side-chain oxygen of the active site serine, Ser195. The boron adopts a nearly tetrahedral geometry, and the boronic acid forms a set of interactions with the protein that mimic the tetrahedral transition state of serine proteases. Contributions of the arginine side chain to inhibitor affinity were examined by synthesis of the ornithine, lysine, homolysine, and amidine analogs of DuP714. The basic groups interact with backbone carbonyl groups, water molecules, and an aspartic acid side chain (Asp189) located in the thrombin S1 specificity pocket. The variation in inhibition constant by 3 orders of magnitude appears to reflect differences in the energetics of interactions made with thrombin and differences in ligand flexibility in solution.(ABSTRACT TRUNCATED AT 250 WORDS) |
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1LHD is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Hirudo_medicinalis Hirudo medicinalis] and [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with DI2 as [http://en.wikipedia.org/wiki/ligand ligand]. 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:// | + | 1LHD is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Hirudo_medicinalis Hirudo medicinalis] and [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=DI2:'>DI2</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. 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=1LHD OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Protein complex]] | [[Category: Protein complex]] | ||
[[Category: Thrombin]] | [[Category: Thrombin]] | ||
| - | [[Category: Chang, C | + | [[Category: Chang, C H.]] |
| - | [[Category: Kettner, C | + | [[Category: Kettner, C A.]] |
| - | [[Category: Lee, S | + | [[Category: Lee, S L.]] |
| - | [[Category: Lewandowski, F | + | [[Category: Lewandowski, F A.]] |
| - | [[Category: Schadt, M | + | [[Category: Schadt, M C.]] |
| - | [[Category: Weber, P | + | [[Category: Weber, P C.]] |
[[Category: DI2]] | [[Category: DI2]] | ||
[[Category: acute phase]] | [[Category: acute phase]] | ||
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[[Category: zymogen]] | [[Category: zymogen]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:45:00 2008'' |
Revision as of 11:45, 21 February 2008
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HUMAN ALPHA-THROMBIN COMPLEXED WITH AC-(D)PHE-PRO-BOROLYS-OH
Contents |
Overview
The X-ray crystallographic structure of Ac-(D)Phe-Pro-boroArg-OH [DuP714, Ki = 0.04 nM; Kettner, C., Mersinger, L., & Knabb, R. (1990) J. Biol. Chem. 265, 18289] complexed with human alpha-thrombin shows the boron atom covalently bonded to the side-chain oxygen of the active site serine, Ser195. The boron adopts a nearly tetrahedral geometry, and the boronic acid forms a set of interactions with the protein that mimic the tetrahedral transition state of serine proteases. Contributions of the arginine side chain to inhibitor affinity were examined by synthesis of the ornithine, lysine, homolysine, and amidine analogs of DuP714. The basic groups interact with backbone carbonyl groups, water molecules, and an aspartic acid side chain (Asp189) located in the thrombin S1 specificity pocket. The variation in inhibition constant by 3 orders of magnitude appears to reflect differences in the energetics of interactions made with thrombin and differences in ligand flexibility in solution.(ABSTRACT TRUNCATED AT 250 WORDS)
Disease
Known diseases associated with this structure: Dysprothrombinemia OMIM:[176930], Hyperprothrombinemia OMIM:[176930], Hypoprothrombinemia OMIM:[176930]
About this Structure
1LHD is a Protein complex structure of sequences from Hirudo medicinalis and Homo sapiens with as ligand. Active as Thrombin, with EC number 3.4.21.5 Full crystallographic information is available from OCA.
Reference
Kinetic and crystallographic studies of thrombin with Ac-(D)Phe-Pro-boroArg-OH and its lysine, amidine, homolysine, and ornithine analogs., Weber PC, Lee SL, Lewandowski FA, Schadt MC, Chang CW, Kettner CA, Biochemistry. 1995 Mar 21;34(11):3750-7. PMID:7893672
Page seeded by OCA on Thu Feb 21 13:45:00 2008
Categories: Hirudo medicinalis | Homo sapiens | Protein complex | Thrombin | Chang, C H. | Kettner, C A. | Lee, S L. | Lewandowski, F A. | Schadt, M C. | Weber, P C. | DI2 | Acute phase | Blood coagulation | Calcium-binding | Complex (serine protease/inhibitor) | Disease mutation | Duplication | Gamma-carboxyglutamic acid | Glycoprotein | Hydrolase | Kringle | Liver | Plasma | Serine protease | Signal | Vitamin k | Zymogen
