3CV1

Atomic Resolution Structures of Escherichia coli and Bacillis anthracis Malate Synthase A: Comparison with Isoform G and Implications for Structure Based Drug Design

3CV1 の概要

• エントリーDOI: 10.2210/pdb3cv1/pdb
• 関連するPDBエントリー: 1D8C 3CUX 3CUZ 3CV2
• 分子名称: Malate synthase A, CALCIUM ION, ACETATE ION, ... (5 entities in total)
• 機能のキーワード: malate synthase, tim barrel, glyoxylate bypass, transferase, tricarboxylic acid cycle
• 由来する生物種: Escherichia coli
• 細胞内の位置: Cytoplasm: P08997
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 60442.44

構造登録者

Lohman, J.R. (登録日: 2008-04-17, 公開日: 2008-11-11, 最終更新日: 2024-02-21)

主引用文献

Lohman, J.R.,Olson, A.C.,Remington, S.J.
Atomic resolution structures of Escherichia coli and Bacillus anthracis malate synthase A: comparison with isoform G and implications for structure-based drug discovery
Protein Sci., 17:1935-1945, 2008

PubMed Abstract: Enzymes of the glyoxylate shunt are important for the virulence of pathogenic organisms such as Mycobacterium tuberculosis and Candida albicans. Two isoforms have been identified for malate synthase, the second enzyme in the pathway. Isoform A, found in fungi and plants, comprises approximately 530 residues, whereas isoform G, found only in bacteria, is larger by approximately 200 residues. Crystal structures of malate synthase isoform G from Escherichia coli and Mycobacterium tuberculosis were previously determined at moderate resolution. Here we describe crystal structures of E. coli malate synthase A (MSA) in the apo form (1.04 A resolution) and in complex with acetyl-coenzyme A and a competitive inhibitor, possibly pyruvate or oxalate (1.40 A resolution). In addition, a crystal structure for Bacillus anthracis MSA at 1.70 A resolution is reported. The increase in size between isoforms A and G can be attributed primarily to an inserted alpha/beta domain that may have regulatory function. Upon binding of inhibitor or substrate, several active site loops in MSA undergo large conformational changes. However, in the substrate bound form, the active sites of isoforms A and G from E. coli are nearly identical. Considering that inhibitors bind with very similar affinities to both isoforms, MSA is as an excellent platform for high-resolution structural studies and drug discovery efforts.

PubMed: 18714089
DOI: 10.1110/ps.036269.108

実験手法

X-RAY DIFFRACTION (1.68 Å)