1LHF: Human Alpha-Thrombin Complexed With Ac-(D)phe-Pro-Boro- Homolys-Oh

Citation:
Abstract
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)
PDB ID: 1LHFDownload
MMDB ID: 5689
PDB Deposition Date: 1994/12/27
Updated in MMDB: 1998/11
Experimental Method:
x-ray diffraction
Resolution: 2.4  Å
Source Organism:
Homo sapiens
Similar Structures:
Biological Unit for 1LHF: trimeric; determined by author
Molecular Components in 1LHF
Label Count Molecule
Proteins (3 molecules)
1
Alpha-thrombin(Gene symbol: F2)
Molecule annotation
1
Alpha-thrombin(Gene symbol: F2)
Molecule annotation
1
Hirudin
Molecule annotation
Chemical (1 molecule)
1
1
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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