1lhc

File:1lhc.gif

spinqualitylabelsall models 1lhc, resolution 1.95Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

HUMAN ALPHA-THROMBIN COMPLEXED WITH AC-(D)PHE-PRO-BOROARG-OH

OverviewOverview

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)

DiseaseDisease

Known diseases associated with this structure: Dysprothrombinemia OMIM:[176930], Hyperprothrombinemia OMIM:[176930], Hypoprothrombinemia OMIM:[176930]

About this StructureAbout this Structure

1LHC is a Protein complex structure of sequences from Hirudo medicinalis and Homo sapiens with DP7 as ligand. Active as Thrombin, with EC number 3.4.21.5 Full crystallographic information is available from OCA.

ReferenceReference

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

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