1DIT

COMPLEX OF A DIVALENT INHIBITOR WITH THROMBIN

1DIT の概要

• エントリーDOI: 10.2210/pdb1dit/pdb
• 分子名称: ALPHA-THROMBIN, PEPTIDE INHIBITOR CVS995, ... (4 entities in total)
• 機能のキーワード: hydrolase, blood coagulation, inhibitor, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Secreted, extracellular space: P00734 P00734
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 36010.99

構造登録者

Tulinsky, A.,Krishnan, R. (登録日: 1995-07-20, 公開日: 1996-06-10, 最終更新日: 2023-11-15)

主引用文献

Krishnan, R.,Tulinsky, A.,Vlasuk, G.P.,Pearson, D.,Vallar, P.,Bergum, P.,Brunck, T.K.,Ripka, W.C.
Synthesis, structure, and structure-activity relationships of divalent thrombin inhibitors containing an alpha-keto-amide transition-state mimetic.
Protein Sci., 5:422-433, 1996

PubMed Abstract: A new class of divalent thrombin inhibitors is described that contains an alpha-keto-amide transition-state mimetic linking an active site binding group and a group that binds to the fibrinogen-binding exosite. The X-ray crystallographic structure of the most potent member of this new class, CVS995, shows many features in common with other divalent thrombin inhibitors and clearly defines the transition-state-like binding of the alpha-keto-amide group. The structure of the active site part of the inhibitor shows a network of water molecules connecting both the side-chain and backbone atoms of thrombin and the inhibitor. Direct peptide analogues of the new transition-state-containing divalent thrombin inhibitors were compared using in vitro assays of thrombin inhibition. There was no direct correlation between the binding constants of the peptides and their alpha-keto-amide counterparts. The most potent alpha-keto-amide inhibitor, CVS995, with a Ki = 1 pM, did not correspond to the most potent divalent peptide and contained a single amino acid deletion in the exosite binding region with respect to the equivalent region of the natural thrombin inhibitor hirudin. The interaction energies of the active site, transition state, and exosite binding regions of these new divalent thrombin inhibitors are not additive.

PubMed: 8868478

実験手法

X-RAY DIFFRACTION (2.3 Å)