1YBT

MYCOBACTERIUM TUBERCULOSIS ADENYLYL CYCLASE, RV1900C CHD

1YBT の概要

• エントリーDOI: 10.2210/pdb1ybt/pdb
• 関連するPDBエントリー: 1ybu
• 分子名称: hydrolase, alpha/beta hydrolase fold family (2 entities in total)
• 機能のキーワード: cyclase homology domain, chd, rv1900c, hydrolase
• 由来する生物種: Mycobacterium tuberculosis
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 79839.17

構造登録者

Sinha, S.C.,Wetterer, M.,Sprang, S.R.,Schultz, J.E.,Linder, J.U. (登録日: 2004-12-21, 公開日: 2005-02-15, 最終更新日: 2024-11-13)

主引用文献

Sinha, S.C.,Wetterer, M.,Sprang, S.R.,Schultz, J.E.,Linder, J.U.
Origin of asymmetry in adenylyl cyclases: structures of Mycobacterium tuberculosis Rv1900c.
Embo J., 24:663-673, 2005

PubMed Abstract: Rv1900c, a Mycobacterium tuberculosis adenylyl cyclase, is composed of an N-terminal alpha/beta-hydrolase domain and a C-terminal cyclase homology domain. It has an unusual 7% guanylyl cyclase side-activity. A canonical substrate-defining lysine and a catalytic asparagine indispensable for mammalian adenylyl cyclase activity correspond to N342 and H402 in Rv1900c. Mutagenic analysis indicates that these residues are dispensable for activity of Rv1900c. Structures of the cyclase homology domain, solved to 2.4 A both with and without an ATP analog, form isologous, but asymmetric homodimers. The noncanonical N342 and H402 do not interact with the substrate. Subunits of the unliganded open dimer move substantially upon binding substrate, forming a closed dimer similar to the mammalian cyclase heterodimers, in which one interfacial active site is occupied and the quasi-dyad-related active site is occluded. This asymmetry indicates that both active sites cannot simultaneously be catalytically active. Such a mechanism of half-of-sites-reactivity suggests that mammalian heterodimeric adenylyl cyclases may have evolved from gene duplication of a primitive prokaryote-type cyclase, followed by loss of function in one active site.

PubMed: 15678099
DOI: 10.1038/sj.emboj.7600573

実験手法

X-RAY DIFFRACTION (2.31 Å)