7E51

Structure of PEP bound Enolase from Mycobacterium tuberculosis

Summary for 7E51

• Entry DOI: 10.2210/pdb7e51/pdb
• Related: 7CLL
• EMDB information: 30989
• Descriptor: Enolase, PHOSPHOENOLPYRUVATE, MAGNESIUM ION (3 entities in total)
• Functional Keywords: metal binding protein
• Biological source: Mycobacterium tuberculosis
• Total number of polymer chains: 8
• Total formula weight: 369432.06

Authors

Bose, S.,Vinothkumar, K.R. (deposition date: 2021-02-16, release date: 2022-02-16, Last modification date: 2023-11-08)

Primary citation

Ahmad, M.,Jha, B.,Bose, S.,Tiwari, S.,Dwivedy, A.,Kar, D.,Pal, R.,Mariadasse, R.,Parish, T.,Jeyakanthan, J.,Vinothkumar, K.R.,Biswal, B.K.
Structural snapshots of Mycobacterium tuberculosis enolase reveal dual mode of 2PG binding and its implication in enzyme catalysis.
Iucrj, 10:738-753, 2023

PubMed Abstract: Enolase, a ubiquitous enzyme, catalyzes the reversible conversion of 2-phosphoglycerate (2PG) to phosphoenolpyruvate (PEP) in the glycolytic pathway of organisms of all three domains of life. The underlying mechanism of the 2PG to PEP conversion has been studied in great detail in previous work, however that of the reverse reaction remains to be explored. Here we present structural snapshots of Mycobacterium tuberculosis (Mtb) enolase in apo, PEP-bound and two 2PG-bound forms as it catalyzes the conversion of PEP to 2PG. The two 2PG-bound complex structures differed in the conformation of the bound product (2PG) viz the widely reported canonical conformation and a novel binding pose, which we refer to here as the alternate conformation. Notably, we observed two major differences compared with the forward reaction: the presence of Mg is non-obligatory for the reaction and 2PG assumes an alternate conformation that is likely to facilitate its dissociation from the active site. Molecular dynamics studies and binding free energy calculations further substantiate that the alternate conformation of 2PG causes distortions in both metal ion coordination and hydrogen-bonding interactions, resulting in an increased flexibility of the active-site loops and aiding product release. Taken together, this study presents a probable mechanism involved in PEP to 2PG catalysis that is likely to be mediated by the conformational change of 2PG at the active site.

PubMed: 37860976
DOI: 10.1107/S2052252523008485

Experimental method

ELECTRON MICROSCOPY (3.23 Å)