4Y12

Crystal structure of the S/T protein kinase PknG from Mycobacterium tuberculosis in complex with AGS

4Y12 の概要

• エントリーDOI: 10.2210/pdb4y12/pdb
• 関連するPDBエントリー: 4Y0X
• 分子名称: Serine/threonine-protein kinase PknG, PHOSPHOTHIOPHOSPHORIC ACID-ADENYLATE ESTER, ZINC ION, ... (5 entities in total)
• 機能のキーワード: s/t protein kinase, pkng, transferase
• 由来する生物種: Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
• 細胞内の位置: Cytoplasm: P9WI73
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 41596.60

構造登録者

Lisa, M.N.,Alzari, P.M. (登録日: 2015-02-06, 公開日: 2015-05-20, 最終更新日: 2024-01-10)

主引用文献

Lisa, M.N.,Gil, M.,Andre-Leroux, G.,Barilone, N.,Duran, R.,Biondi, R.M.,Alzari, P.M.
Molecular Basis of the Activity and the Regulation of the Eukaryotic-like S/T Protein Kinase PknG from Mycobacterium tuberculosis.
Structure, 23:1039-1048, 2015

PubMed Abstract: Tuberculosis remains one of the world's deadliest human diseases, with a high prevalence of antibiotic-resistant Mycobacterium tuberculosis (Mtb) strains. A molecular understanding of processes underlying regulation and adaptation of bacterial physiology may provide novel avenues for the development of antibiotics with unconventional modes of action. Here, we focus on the multidomain S/T protein kinase PknG, a soluble enzyme that controls central metabolism in Actinobacteria and has been linked to Mtb infectivity. Our biochemical and structural studies reveal how different motifs and domains flanking the catalytic core regulate substrate selectivity without significantly affecting the intrinsic kinase activity, whereas a rubredoxin-like domain is shown to downregulate catalysis through specific intramolecular interactions that modulate access to a profound substrate-binding site. Our findings provide the basis for the selective and specific inhibition of PknG, and open new questions about regulation of related bacterial and eukaryotic protein kinases.

PubMed: 25960409
DOI: 10.1016/j.str.2015.04.001

実験手法

X-RAY DIFFRACTION (1.9 Å)