5WS9

Pyruvate kinase (PYK) from Mycobacterium tuberculosis in complex with Oxalate, ATP and allosteric activator AMP

Summary for 5WS9

• Entry DOI: 10.2210/pdb5ws9/pdb
• Related: 5WRP 5WS8 5WSA 5WSB 5WSC
• Descriptor: Pyruvate kinase, MAGNESIUM ION, OXALATE ION, ... (8 entities in total)
• Functional Keywords: pyruvate kinase, glycolysis, tetramer, allostery, synergism, phospho transferase, transferase
• Biological source: Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
• Total number of polymer chains: 4
• Total formula weight: 208470.04

Authors

Zhong, W.,Cai, Q.,El Sahili, A.,Lescar, J.,Dedon, P.C. (deposition date: 2016-12-06, release date: 2017-11-15, Last modification date: 2023-11-08)

Primary citation

Zhong, W.,Cui, L.,Goh, B.C.,Cai, Q.,Ho, P.,Chionh, Y.H.,Yuan, M.,Sahili, A.E.,Fothergill-Gilmore, L.A.,Walkinshaw, M.D.,Lescar, J.,Dedon, P.C.
Allosteric pyruvate kinase-based "logic gate" synergistically senses energy and sugar levels in Mycobacterium tuberculosis.
Nat Commun, 8:1986-1986, 2017

PubMed Abstract: Pyruvate kinase (PYK) is an essential glycolytic enzyme that controls glycolytic flux and is critical for ATP production in all organisms, with tight regulation by multiple metabolites. Yet the allosteric mechanisms governing PYK activity in bacterial pathogens are poorly understood. Here we report biochemical, structural and metabolomic evidence that Mycobacterium tuberculosis (Mtb) PYK uses AMP and glucose-6-phosphate (G6P) as synergistic allosteric activators that function as a molecular "OR logic gate" to tightly regulate energy and glucose metabolism. G6P was found to bind to a previously unknown site adjacent to the canonical site for AMP. Kinetic data and structural network analysis further show that AMP and G6P work synergistically as allosteric activators. Importantly, metabolome profiling in the Mtb surrogate, Mycobacterium bovis BCG, reveals significant changes in AMP and G6P levels during nutrient deprivation, which provides insights into how a PYK OR gate would function during the stress of Mtb infection.

PubMed: 29215013
DOI: 10.1038/s41467-017-02086-y

Experimental method

X-RAY DIFFRACTION (1.9 Å)