5ZON

Histidinol phosphate phosphatase from Mycobacterium tuberculosis

5ZON の概要

• エントリーDOI: 10.2210/pdb5zon/pdb
• 分子名称: Histidinol-phosphatase, ZINC ION, PHOSPHATE ION, ... (5 entities in total)
• 機能のキーワード: phosphatase, histidine biosynthetic pathway, 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: 116075.87

構造登録者

Jha, B.,Kumar, D.,Biswal, B.K. (登録日: 2018-04-13, 公開日: 2018-05-23, 最終更新日: 2023-11-22)

主引用文献

Jha, B.,Kumar, D.,Sharma, A.,Dwivedy, A.,Singh, R.,Biswal, B.K.
Identification and structural characterization of a histidinol phosphate phosphatase from Mycobacterium tuberculosis
J. Biol. Chem., 293:10102-10118, 2018

PubMed Abstract: The absence of a histidine biosynthesis pathway in humans, coupled with histidine essentiality for survival of the important human pathogen (), underscores the importance of the bacterial enzymes of this pathway as major antituberculosis drug targets. However, the identity of the mycobacterial enzyme that functions as the histidinol phosphate phosphatase (HolPase) of this pathway remains to be established. Here, we demonstrate that the enzyme encoded by the gene, belonging to the inositol monophosphatase (IMPase) family, functions as the HolPase and specifically dephosphorylates histidinol phosphate. The crystal structure of Rv3137 in apo form enabled us to dissect its distinct structural features. Furthermore, the holo-complex structure revealed that a unique cocatalytic multizinc-assisted mode of substrate binding and catalysis is the hallmark of HolPase. Interestingly, the enzyme-substrate complex structure unveiled that although monomers possess individual catalytic sites they share a common product-exit channel at the dimer interface. Furthermore, target-based screening against HolPase identified several small-molecule inhibitors of this enzyme. Taken together, our study unravels the missing enzyme link in the histidine biosynthesis pathway, augments our current mechanistic understanding of histidine production in , and has helped identify potential inhibitors of this bacterial pathway.

PubMed: 29752410
DOI: 10.1074/jbc.RA118.002299

実験手法

X-RAY DIFFRACTION (1.94 Å)