1d4p
From Proteopedia
(New page: 200px<br /> <applet load="1d4p" size="450" color="white" frame="true" align="right" spinBox="true" caption="1d4p, resolution 2.07Å" /> '''CRYSTAL STRUCTURE O...) |
|||
| Line 1: | Line 1: | ||
| - | [[Image:1d4p. | + | [[Image:1d4p.jpg|left|200px]]<br /><applet load="1d4p" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1d4p" size=" | + | |
caption="1d4p, resolution 2.07Å" /> | caption="1d4p, resolution 2.07Å" /> | ||
'''CRYSTAL STRUCTURE OF HUMAN ALPHA THROMBIN IN COMPLEX WITH 5-AMIDINOINDOLE-4-BENZYLPIPERIDINE INHIBITOR'''<br /> | '''CRYSTAL STRUCTURE OF HUMAN ALPHA THROMBIN IN COMPLEX WITH 5-AMIDINOINDOLE-4-BENZYLPIPERIDINE INHIBITOR'''<br /> | ||
| Line 11: | Line 10: | ||
==About this Structure== | ==About this Structure== | ||
| - | 1D4P 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 NAG, NA and BPP 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:// | + | 1D4P 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=NAG:'>NAG</scene>, <scene name='pdbligand=NA:'>NA</scene> and <scene name='pdbligand=BPP:'>BPP</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=1D4P OCA]. |
==Reference== | ==Reference== | ||
| Line 26: | Line 25: | ||
[[Category: thrombin; nonpeptidyl inhibitor; structure-based drug design]] | [[Category: thrombin; nonpeptidyl inhibitor; structure-based drug design]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri Feb 15 15:38:29 2008'' |
Revision as of 13:38, 15 February 2008
|
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 with , and as ligands. Active as Thrombin, with EC number 3.4.21.5 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 Fri Feb 15 15:38:29 2008
