1PFG

Strategy to design inhibitors: Structure of a complex of Proteinase K with a designed octapeptide inhibitor N-Ac-Pro-Ala-Pro-Phe-DAla-Ala-Ala-Ala-NH2 at 2.5A resolution

1PFG の概要

• エントリーDOI: 10.2210/pdb1pfg/pdb
• 分子名称: Proteinase K, N-Ac-PAPFAAAA-NH2 (3 entities in total)
• 機能のキーワード: proteinase k, octapeptide, inhibitor, complex, hydrolase, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 由来する生物種: Engyodontium album; 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 29697.69

構造登録者

Saxena, A.K.,Singh, T.P.,Peters, K.,Fittkau, S.,Betzel, C. (登録日: 2003-05-27, 公開日: 2003-06-10, 最終更新日: 2024-10-30)

主引用文献

Saxena, A.K.,Singh, T.P.,Peters, K.,Fittkau, S.,Betzel, C.
Strategy to design peptide inhibitors: structure of a complex of proteinase K with a designed octapeptide inhibitor N-Ac-Pro-Ala-Pro-Phe-DAla-Ala-Ala-Ala-NH2 at 2.5 A resolution.
Protein Sci., 5:2453-2458, 1996

PubMed Abstract: The crystal structure of a complex formed by the interaction between proteinase K and a designed octapeptide amide, N-Ac-Pro-Ala-Pro-Phe-DAla-Ala-Ala-Ala-NH2, has been determined at 2.5 A resolution and refined to an R-factor of 16.7% for 7,430 reflections in the resolution range of 8.0-2.50 A. The inhibitor forms a stable complex through a series of hydrogen bonds and hydrophobic interactions with the protein atoms and water molecules. The inhibitor is hydrolyzed between Phe4I and DAla5I (I indicates the inhibitor). The two fragments are separated by a distance of 3.2 A between the carbonyl carbon of Phe4I and the main-chain nitrogen of DAla5I. The N-terminal tetrapeptide occupies subsites S1-S5 (S5 for acetyl group), whereas the C-terminal part fits into S1'-S5' region (S5' for amide group). It is the first time that such an extended electron density for a designed synthetic peptide inhibitor has been observed in the prime region of an enzyme of the subtilisin family. In fact, the inhibitor fills the recognition site completely. There is only a slight rearrangement of the protein residues to accommodate the inhibitor. Superposition of the present octapeptide inhibitor on the hexapeptide inhibitor studied previously shows an overall homology of the two inhibitors, although the individual atoms are displaced significantly. It suggests the existence of a recognition site with flexible dimensions. Kinetic studies indicate an inhibition rate of 100% by this specifically designed peptide inhibitor.

PubMed: 8976553
DOI: 10.1002/pro.5560051207

実験手法

X-RAY DIFFRACTION (2.5 Å)