1JQ6

HUMAN CYTOMEGALOVIRUS PROTEASE DIMER-INTERFACE MUTANT, S225Y

1JQ6 の概要

• エントリーDOI: 10.2210/pdb1jq6/pdb
• 関連するPDBエントリー: 1JQ7 1WPO 2WPO
• 分子名称: ASSEMBLIN (2 entities in total)
• 機能のキーワード: herpesvirus, cytomegalovirus, serine protease, dimerization, enzyme activity regulation, hydrolase
• 由来する生物種: Human herpesvirus 5 (Human cytomegalovirus)
• 細胞内の位置: Protease precursor: Host cytoplasm. Assemblin: Host nucleus. Assembly protein: Host nucleus: P16753
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 28518.59

構造登録者

Batra, R.,Khayat, R.,Tong, L. (登録日: 2001-08-03, 公開日: 2001-09-12, 最終更新日: 2024-10-30)

主引用文献

Batra, R.,Khayat, R.,Tong, L.
Molecular mechanism for dimerization to regulate the catalytic activity of human cytomegalovirus protease.
Nat.Struct.Biol., 8:810-817, 2001

PubMed Abstract: Biochemical studies indicate that dimerization is required for the catalytic activity of herpesvirus proteases, whereas structural studies show a complete active site in each monomer, away from the dimer interface. Here we report kinetic, biophysical and crystallographic characterizations of structure-based mutants in the dimer interface of human cytomegalovirus (HCMV) protease. Such mutations can produce a 1,700-fold reduction in the kcat while having minimal effects on the K(m). Dimer stability is not affected by these mutations, suggesting that dimerization itself is insufficient for activity. There are large changes in monomer conformation and dimer organization of the apo S225Y mutant enzyme. However, binding of an activated peptidomimetic inhibitor induced a conformation remarkably similar to the wild type protease. Our studies suggest that appropriate dimer formation may be required to indirectly stabilize the protease oxyanion hole, revealing a novel mechanism for dimerization to regulate enzyme activity.

PubMed: 11524687
DOI: 10.1038/nsb0901-810

実験手法

X-RAY DIFFRACTION (2.3 Å)