1D4P: Crystal Structure Of Human Alpha Thrombin In Complex With 5- Amidinoindole-4-benzylpiperidine Inhibitor

Citation:
Abstract
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).
PDB ID: 1D4PDownload
MMDB ID: 11408
PDB Deposition Date: 1999/10/4
Updated in MMDB: 1999/11
Experimental Method:
x-ray diffraction
Resolution: 2.07  Å
Source Organism:
Homo sapiens
Similar Structures:
Biological Unit for 1D4P: trimeric; determined by author
Molecular Components in 1D4P
Label Count Molecule
Proteins (3 molecules)
1
Alpha-thrombin(Gene symbol: F2)
Molecule annotation
1
Alpha-thrombin(Gene symbol: F2)
Molecule annotation
1
Hirugen
Molecule annotation
Chemicals (4 molecules)
1
1
2
2
3
1
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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