1P03

STRUCTURE ANALYSIS OF SPECIFICITY. ALPHA-LYTIC PROTEASE COMPLEXES WITH ANALOGUES OF REACTION INTERMEDIATES

1P03 の概要

• エントリーDOI: 10.2210/pdb1p03/pdb
• 関連するBIRD辞書のPRD_ID: PRD_000316
• 分子名称: ALPHA-LYTIC PROTEASE, METHOXYSUCCINYL-ALA-ALA-PRO-VALINE BORONIC ACID INHIBITOR, SULFATE ION, ... (4 entities in total)
• 機能のキーワード: hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 由来する生物種: Lysobacter enzymogenes
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 20441.52

構造登録者

Bone, R.,Agard, D.A. (登録日: 1989-04-24, 公開日: 1990-04-15, 最終更新日: 2024-10-09)

主引用文献

Bone, R.,Frank, D.,Kettner, C.A.,Agard, D.A.
Structural analysis of specificity: alpha-lytic protease complexes with analogues of reaction intermediates.
Biochemistry, 28:7600-7609, 1989

PubMed Abstract: To better understand the structural basis of enzyme specificity, the structures of complexes formed between alpha-lytic protease, an extracellular serine protease of Lysobacter enzymogenes, and five inhibitory peptide boronic acids (R2-boroX, where R2 is methoxysuccinyl-Ala-Ala-Pro- and boroX is the alpha-aminoboronic acid analogue of Ala, Val, Ile, Norleu, or Phe) have been studied at high resolution by X-ray crystallography. The enzyme has primary specificity for Ala in the P1 position of peptide substrates with catalytic efficiency decreasing with increasing side-chain volume. Enzyme affinity for inhibitors with boroVal, boroIle, and boroPhe residues is much higher than expected on the basis of the catalytic efficiencies of homologous substrates. Covalent tetrahedral adducts are formed between the active-site serine and the boronic acid moieties of R2-boroAla, R2-boroVal R2-boroIle, and R2-boroNorleu. Though R2-boroVal is a slowly bound inhibitor and R2-boroAla is rapidly bound [Kettner, C. A., Bone, R., Agard, D. A., & Bachovchin, W. W. (1988) Biochemistry 27, 7682-7688], there appear to be no structural differences that could account for slow binding. The removal from solution of 20% more hydrophobic surface on binding accounts for the improved affinity of alpha-lytic protease for R2-boroVal relative to R2-boroAla. The high affinity of the enzyme for R2-boroIle derives from the selective binding of the L-allo stereoisomer of the boroIle residue, which can avoid bad steric interactions in the binding pocket.(ABSTRACT TRUNCATED AT 250 WORDS)

PubMed: 2611204
DOI: 10.1021/bi00445a015

実験手法

X-RAY DIFFRACTION (2.15 Å)