1QRP

Human pepsin 3A in complex with a phosphonate inhibitor IVA-VAL-VAL-LEU(P)-(O)PHE-ALA-ALA-OME

1QRP の概要

• エントリーDOI: 10.2210/pdb1qrp/pdb
• 関連するBIRD辞書のPRD_ID: PRD_000657
• 分子名称: PEPSIN 3A, methyl N-[(2S)-2-({(S)-hydroxy[(1R)-3-methyl-1-{[N-(3-methylbutanoyl)-L-valyl-L-valyl]amino}butyl]phosphoryl}oxy)-3-phenylpropanoyl]-L-alanyl-L-alaninate (3 entities in total)
• 機能のキーワード: aspartic proteinase, phosphonate inhibitor, transition state analogue, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 35385.75

構造登録者

Fujinaga, M.,Cherney, M.M.,Tarasova, N.I.,Bartlett, P.A.,Hanson, J.E.,James, M.N.G. (登録日: 1999-06-15, 公開日: 1999-06-18, 最終更新日: 2024-10-16)

主引用文献

Fujinaga, M.,Cherney, M.M.,Tarasova, N.I.,Bartlett, P.A.,Hanson, J.E.,James, M.N.
Structural study of the complex between human pepsin and a phosphorus-containing peptidic -transition-state analog.
Acta Crystallogr.,Sect.D, 56:272-279, 2000

PubMed Abstract: The refined crystal structure of the complex between human pepsin and a synthetic phosphonate inhibitor, Iva-Val-Val-Leu(P)-(O)Phe-Ala-Ala-OMe [Iva = isovaleryl, Leu(P) = the phosphinic acid analog of L-leucine, (O)Phe = L-3-phenyllactic acid, OMe = methyl ester], is presented. The structure was refined using diffraction data between 30 and 1.96 A resolution to a final R factor ( summation operator| |F(o)| - |F(c)| | / summation operator|F(o)|, where |F(o)| and |F(c)| are the observed and calculated structure-factor amplitudes, respectively) of 20.0%. The interactions of the inhibitor with the enzyme show the locations of the binding sites on the enzyme from S4 to S3'. Modeling of the inhibitor binding to porcine pepsin shows very similar binding sites, except at S4. Comparison of the complex structure with the structures of related inhibitors bound to penicillopepsin helps to rationalize the observed differences in the binding constants. The convergence of reaction mechanisms and geometries in different families of proteinases is also discussed.

PubMed: 10713513
DOI: 10.1107/S0907444999016376

実験手法

X-RAY DIFFRACTION (1.96 Å)