1KPI

Crystal Structure of mycolic acid cyclopropane synthase CmaA2 complexed with SAH and DDDMAB

1KPI の概要

• エントリーDOI: 10.2210/pdb1kpi/pdb
• 関連するPDBエントリー: 1KP9 1KPG 1KPH
• 分子名称: CYCLOPROPANE-FATTY-ACYL-PHOSPHOLIPID SYNTHASE 2, CARBONATE ION, SULFATE ION, ... (6 entities in total)
• 機能のキーワード: mixed alpha beta fold, structural genomics, psi, protein structure initiative, tb structural genomics consortium, tbsgc, transferase
• 由来する生物種: Mycobacterium tuberculosis
• 細胞内の位置: Cytoplasm: P0A5P0
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 35797.32

構造登録者

Huang, C.-C.,Smith, C.V.,Jacobs Jr., W.R.,Glickman, M.S.,Sacchettini, J.C.,TB Structural Genomics Consortium (TBSGC) (登録日: 2001-12-30, 公開日: 2002-01-11, 最終更新日: 2024-02-14)

主引用文献

Huang, C.-C.,Smith, C.V.,Glickman, M.S.,Jacobs Jr., W.R.,Sacchettini, J.C.
Crystal structures of mycolic acid cyclopropane synthases from Mycobacterium tuberculosis
J.Biol.Chem., 277:11559-11569, 2002

PubMed Abstract: Mycolic acids are major components of the cell wall of Mycobacterium tuberculosis. Several studies indicate that functional groups in the acyl chain of mycolic acids are important for pathogenesis and persistence. There are at least three mycolic acid cyclopropane synthases (PcaA, CmaA1, and CmaA2) that are responsible for these site-specific modifications of mycolic acids. To derive information on the specificity and enzyme mechanism of the family of proteins, the crystal structures of CmaA1, CmaA2, and PcaA were solved to 2-, 2-, and 2.65-A resolution, respectively. All three enzymes have a seven-stranded alpha/beta fold similar to other methyltransferases with the location and interactions with the cofactor S-adenosyl-l-methionine conserved. The structures of the ternary complexes demonstrate the position of the mycolic acid substrate binding site. Close examination of the active site reveals electron density that we believe represents a bicarbonate ion. The structures support the hypothesis that these enzymes catalyze methyl transfer via a carbocation mechanism in which the bicarbonate ion acts as a general base. In addition, comparison of the enzyme structures reveals a possible mechanism for substrate specificity. These structures provide a foundation for rational-drug design, which may lead to the development of new inhibitors effective against persistent bacteria.

PubMed: 11756461
DOI: 10.1074/jbc.M111698200

実験手法

X-RAY DIFFRACTION (2.65 Å)