1H8D

X-ray structure of the human alpha-thrombin complex with a tripeptide phosphonate inhibitor.

1H8D の概要

• エントリーDOI: 10.2210/pdb1h8d/pdb
• 関連するPDBエントリー: 1A2C 1A3B 1A3E 1A46 1A4W 1A5G 1A61 1ABI 1ABJ 1AD8 1AE8 1AFE 1AHT 1AI8 1AIX 1AWF 1AWH 1AY6 1B5G 1B7X 1BA8 1BB0 1BCU 1BHX 1BMM 1BMN 1BTH 1C1U 1C1V 1C1W 1C4U 1C4V 1C4Y 1C5L 1C5N 1C5O 1CA8 1D3D 1D3P 1D3Q 1D3T 1D4P 1D6W 1D9I 1DE7 1DIT 1DM4 1DWB 1DWC 1DWD 1DWE 1DX5 1E0F 1EOJ 1EOL 1FPC 1FPH 1HAG 1HAH 1HAI 1HAO 1HAP 1HBT 1HDT 1HGT 1HLT 1HUT 1HXE 1HXF 1IHS 1IHT 1LHC 1LHD 1LHE 1LHF 1LHG 1NRN 1NRO 1NRP 1NRQ 1NRR 1NRS 1PPB 1QBV 1QHR 1QJ1 1QJ6 1QJ7 1QUR 1TBZ 1THP 1THR 1THS 1TMB 1TMT 1TMU 1TOM 1UMA 1UVS 1VR1 2HGT 2HNT 2HPP 2HPQ 2THF 3HAT 3HTC 4HTC 4THN 5GDS 7KME 8KME
• 分子名称: THROMBIN, HIRUDIN I, N-[(benzyloxy)carbonyl]-beta-phenyl-D-phenylalanyl-N-{(1S,3E)-1-[dihydroxy(diphenoxy)-lambda~5~-phosphanyl]-4-methoxybut-3-en-1-yl}-L-prolinamide, ... (5 entities in total)
• 機能のキーワード: serine protease, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 由来する生物種: HOMO SAPIENS (HUMAN); 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 35371.46

構造登録者

Skordalakes, E.,Dodson, G.G.,Green, D.,Deadman, J. (登録日: 2001-02-01, 公開日: 2001-02-26, 最終更新日: 2024-11-13)

主引用文献

Skordalakes, E.,Dodson, G.G.,Green, D.S.,Goodwin, C.A.,Scully, M.F.,Hudson, H.R.,Kakkar, V.V.,Deadman, J.J.
Inhibition of Human Alpha-Thrombin by a Phosphonate Tripeptide Proceeds Via a Metastable Pentacoordinated Phosphorus Intermediate
J.Mol.Biol., 311:549-, 2001

PubMed Abstract: X-ray crystallographic studies of human alpha-thrombin with a novel synthetic inhibitor, an acyl (alpha-aminoalkyl)phosphonate, reveal the existence of a pentacovalent phosphorus intermediate state. Crystal structures of the complex of alpha-thrombin with the phosphonate compound were determined independently using crystals of different ages. The first structure, solved from a crystal less than seven days old, showed a pentacoordinated phosphorus moiety. The second structure, determined from a crystal that was 12 weeks old, showed a tetracoordinated phosphorus moiety. In the first structure, a water molecule, made nucleophilic by coordination to His57 of alpha-thrombin, is bonded to the pentacoordinated phosphorus atom. Its position is approximately equivalent to that occupied by the water molecule responsible for hydrolytic deacylation during normal hydrolysis. The pentacoordinated phosphorus adduct collapses to give the expected pseudo tetrahedral complex, where the phosphorus atom is covalently bonded to Ser195 O(gamma). The crystallographic data presented here therefore suggest that the covalent bond formed between the inhibitor's phosphorus atom and O(gamma) of Ser195 proceeds via an addition-elimination mechanism, which involves the formation of a pentacoordinate intermediate.

PubMed: 11493008
DOI: 10.1006/JMBI.2001.4872

実験手法

X-RAY DIFFRACTION (1.4 Å)