4Y12

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

Summary for 4Y12

• Entry DOI: 10.2210/pdb4y12/pdb
• Related: 4Y0X
• Descriptor: Serine/threonine-protein kinase PknG, PHOSPHOTHIOPHOSPHORIC ACID-ADENYLATE ESTER, ZINC ION, ... (5 entities in total)
• Functional Keywords: s/t protein kinase, pkng, transferase
• Biological source: Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
• Cellular location: Cytoplasm: P9WI73
• Total number of polymer chains: 1
• Total formula weight: 41596.60

Authors

Lisa, M.N.,Alzari, P.M. (deposition date: 2015-02-06, release date: 2015-05-20, Last modification date: 2024-01-10)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.9 Å)