6QXL

Crystal Structure of Pyruvate Kinase II (PykA) from Pseudomonas aeruginosa in complex with sodium malonate, magnesium and glucose-6-phosphate

Summary for 6QXL

• Entry DOI: 10.2210/pdb6qxl/pdb
• Descriptor: Pyruvate kinase, 6-O-phosphono-alpha-D-glucopyranose, MAGNESIUM ION, ... (6 entities in total)
• Functional Keywords: pyruvate kinase, pyka, homotetramer, polypeptide, g6p-bound, pyka-mli-mg complex, transferase
• Biological source: Pseudomonas aeruginosa
• Total number of polymer chains: 12
• Total formula weight: 632825.29

Authors

Abdelhamid, Y.,Brear, P.,Welch, M. (deposition date: 2019-03-07, release date: 2019-09-11, Last modification date: 2024-01-24)

Primary citation

Abdelhamid, Y.,Brear, P.,Greenhalgh, J.,Chee, X.,Rahman, T.,Welch, M.
Evolutionary plasticity in the allosteric regulator-binding site of pyruvate kinase isoform PykA fromPseudomonas aeruginosa.
J.Biol.Chem., 294:15505-15516, 2019

PubMed Abstract: Unlike many other well-characterized bacteria, the opportunistic human pathogen relies exclusively on the Entner-Doudoroff pathway (EDP) for glycolysis. Pyruvate kinase (PK) is the main "pacemaker" of the EDP, and its activity is also relevant for virulence. Two distinct isozymes of bacterial PK have been recognized, PykA and PykF. Here, using growth and expression analyses of relevant PK mutants, we show that PykA is the dominant isoform in Enzyme kinetics assays revealed that PykA displays potent K-type allosteric activation by glucose 6-phosphate and by intermediates from the pentose phosphate pathway. Unexpectedly, the X-ray structure of PykA at 2.4 Å resolution revealed that glucose 6-phosphate binds in a pocket that is distinct from the binding site reported for this metabolite in the PK from (the only other available bacterial PK structure containing bound glucose 6-phosphate). We propose a mechanism by which glucose 6-phosphate binding at the allosteric site communicates with the PykA active site. Taken together, our findings indicate remarkable evolutionary plasticity in the mechanism(s) by which PK senses and responds to allosteric signals.

PubMed: 31484721
DOI: 10.1074/jbc.RA119.009156

Experimental method

X-RAY DIFFRACTION (2.43 Å)