1d4p
From Proteopedia
| Line 1: | Line 1: | ||
| - | [[Image:1d4p.jpg|left|200px]] | + | [[Image:1d4p.jpg|left|200px]] |
| - | + | ||
| - | '''CRYSTAL STRUCTURE OF HUMAN ALPHA THROMBIN IN COMPLEX WITH 5-AMIDINOINDOLE-4-BENZYLPIPERIDINE INHIBITOR''' | + | {{Structure |
| + | |PDB= 1d4p |SIZE=350|CAPTION= <scene name='initialview01'>1d4p</scene>, resolution 2.07Å | ||
| + | |SITE= | ||
| + | |LIGAND= <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene> and <scene name='pdbligand=BPP:(4-BENZYL-PIPERIDIN-1-YL)-(5-AMIDINOMETHYL-3AH-INDOL-2-YL-METHANONE'>BPP</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] | ||
| + | |GENE= | ||
| + | }} | ||
| + | |||
| + | '''CRYSTAL STRUCTURE OF HUMAN ALPHA THROMBIN IN COMPLEX WITH 5-AMIDINOINDOLE-4-BENZYLPIPERIDINE INHIBITOR''' | ||
| + | |||
==Overview== | ==Overview== | ||
| Line 10: | Line 19: | ||
==About this Structure== | ==About this Structure== | ||
| - | 1D4P is a [ | + | 1D4P is a [[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]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1D4P OCA]. |
==Reference== | ==Reference== | ||
| - | The crystal structure of human alpha-thrombin complexed with LY178550, a nonpeptidyl, active site-directed inhibitor., Chirgadze NY, Sall DJ, Klimkowski VJ, Clawson DK, Briggs SL, Hermann R, Smith GF, Gifford-Moore DS, Wery JP, Protein Sci. 1997 Jul;6(7):1412-7. PMID:[http:// | + | The crystal structure of human alpha-thrombin complexed with LY178550, a nonpeptidyl, active site-directed inhibitor., Chirgadze NY, Sall DJ, Klimkowski VJ, Clawson DK, Briggs SL, Hermann R, Smith GF, Gifford-Moore DS, Wery JP, Protein Sci. 1997 Jul;6(7):1412-7. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/9232642 9232642] |
[[Category: Hirudo medicinalis]] | [[Category: Hirudo medicinalis]] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
| Line 25: | Line 34: | ||
[[Category: thrombin; nonpeptidyl inhibitor; structure-based drug design]] | [[Category: thrombin; nonpeptidyl inhibitor; structure-based drug design]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 10:32:50 2008'' |
Revision as of 08:32, 20 March 2008
| |||||||
| , resolution 2.07Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , and | ||||||
| Activity: | Thrombin, with EC number 3.4.21.5 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
CRYSTAL STRUCTURE OF HUMAN ALPHA THROMBIN IN COMPLEX WITH 5-AMIDINOINDOLE-4-BENZYLPIPERIDINE INHIBITOR
Contents |
Overview
The crystal structure of human alpha-thrombin in complex with LY178550, a nonpeptidyl, active site-directed inhibitor, has been solved to 2.07 A resolution by the method of X-ray crystallography. The final model of the complex has a crystallographic R-value of 21.5% (Rfree = 23.1%) with 0.014 A and 2.4 degrees standard deviation from ideal bond lengths and angles, respectively. Well-defined electron density was observed for the inhibitor in the active site. The inhibitor binds to the active site in an L-shaped manner, mimicking the bound conformation of the tripeptide arginal series of thrombin inhibitors (Chirgadze NY et al., 1992, American Crystallographic Association Meeting 20: 116 [Abstr. PB311]). The basic amidine of LY178550 forms a salt bridge with Asp 189 within the specificity pocket, while the 4-benzylpiperidine side chain engages in a number of hydrophobic interactions at the S2 and S3 binding sites. The inhibitor does not interact in any fashion with the active site sequence Ser 214-Gly 216, as occurs with many of the inhibitors studied previously. The indole N-H of the inhibitor forms a hydrogen bond to the gamma-oxygen of the catalytic serine (Ser 195).
Disease
Known diseases associated with this structure: Dysprothrombinemia OMIM:[176930], Hyperprothrombinemia OMIM:[176930], Hypoprothrombinemia OMIM:[176930]
About this Structure
1D4P is a Protein complex structure of sequences from Hirudo medicinalis and Homo sapiens. Full crystallographic information is available from OCA.
Reference
The crystal structure of human alpha-thrombin complexed with LY178550, a nonpeptidyl, active site-directed inhibitor., Chirgadze NY, Sall DJ, Klimkowski VJ, Clawson DK, Briggs SL, Hermann R, Smith GF, Gifford-Moore DS, Wery JP, Protein Sci. 1997 Jul;6(7):1412-7. PMID:9232642
Page seeded by OCA on Thu Mar 20 10:32:50 2008
