4BZQ

Structure of the Mycobacterium tuberculosis APS kinase CysC in complex with ADP and APS

4BZQ の概要

• エントリーDOI: 10.2210/pdb4bzq/pdb
• 関連するPDBエントリー: 4BZP 4BZX
• 分子名称: BIFUNCTIONAL ENZYME CYSN/CYSC, ADENOSINE-5'-PHOSPHOSULFATE, ADENOSINE-5'-DIPHOSPHATE, ... (6 entities in total)
• 機能のキーワード: transferase, sulfur assimilation, adp
• 由来する生物種: MYCOBACTERIUM TUBERCULOSIS
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 40332.65

構造登録者

Poyraz, O.,Schnell, R.,Schneider, G. (登録日: 2013-07-29, 公開日: 2014-08-13, 最終更新日: 2023-12-20)

主引用文献

Poyraz, O.,Brunner, K.,Lohkamp, B.,Axelsson, H.,Hammarstrom, L.G.J.,Schnell, R.,Schneider, G.
Crystal Structures of the Kinase Domain of the Sulfate-Activating Complex in Mycobacterium Tuberculosis.
Plos One, 10:21494-, 2015

PubMed Abstract: In Mycobacterium tuberculosis the sulfate activating complex provides a key branching point in sulfate assimilation. The complex consists of two polypeptide chains, CysD and CysN. CysD is an ATP sulfurylase that, with the energy provided by the GTPase activity of CysN, forms adenosine-5'-phosphosulfate (APS) which can then enter the reductive branch of sulfate assimilation leading to the biosynthesis of cysteine. The CysN polypeptide chain also contains an APS kinase domain (CysC) that phosphorylates APS leading to 3'-phosphoadenosine-5'-phosphosulfate, the sulfate donor in the synthesis of sulfolipids. We have determined the crystal structures of CysC from M. tuberculosis as a binary complex with ADP, and as ternary complexes with ADP and APS and the ATP mimic AMP-PNP and APS, respectively, to resolutions of 1.5 Å, 2.1 Å and 1.7 Å, respectively. CysC shows the typical APS kinase fold, and the structures provide comprehensive views of the catalytic machinery, conserved in this enzyme family. Comparison to the structure of the human homolog show highly conserved APS and ATP binding sites, questioning the feasibility of the design of specific inhibitors of mycobacterial CysC. Residue Cys556 is part of the flexible lid region that closes off the active site upon substrate binding. Mutational analysis revealed this residue as one of the determinants controlling lid closure and hence binding of the nucleotide substrate.

PubMed: 25807013
DOI: 10.1371/JOURNAL.PONE.0121494

実験手法

X-RAY DIFFRACTION (2.1 Å)