4QIJ

Crystal structure of MenB from Mycobacteria tuberculosis in complex with 1-HNA-CoA

Summary for 4QIJ

• Entry DOI: 10.2210/pdb4qij/pdb
• Related: 4QII
• Descriptor: 1,4-Dihydroxy-2-naphthoyl-CoA synthase, 1-hydroxy-2-naphthoyl-CoA (3 entities in total)
• Functional Keywords: 1, 4-dihydroxy-2-naphthoyl-coenzyme a synthase, menb, 1-hna-coa, lyase
• Biological source: Mycobacterium tuberculosis H37Rv
• Total number of polymer chains: 12
• Total formula weight: 454091.99

Authors

Song, H.G.,Sung, H.P.,Tse, Y.S.,Guo, Z.H. (deposition date: 2014-05-31, release date: 2014-11-19, Last modification date: 2023-11-08)

Primary citation

Song, H.,Sung, H.P.,Tse, Y.S.,Jiang, M.,Guo, Z.H.
Ligand-dependent active-site closure revealed in the crystal structure of Mycobacterium tuberculosis MenB complexed with product analogues
Acta Crystallogr.,Sect.D, 70:2959-2969, 2014

PubMed Abstract: 1,4-Dihydroxy-2-naphthoyl coenzyme A (DHNA-CoA) synthase catalyzes an essential intramolecular Claisen condensation in menaquinone biosynthesis and is an important target for the development of new antibiotics. This enzyme in Mycobacterium tuberculosis is cofactor-free and is classified as a type II DHNA-CoA synthase, differing from type I enzymes, which rely on exogenous bicarbonate for catalysis. Its crystal structures in complex with product analogues have been determined at high resolution to reveal ligand-dependent structural changes, which include the ordering of a 27-residue active-site loop (amino acids 107-133) and the reorientation of the carboxy-terminal helix (amino acids 289-301) that forms part of the active site from the opposing subunit across the trimer-trimer interface. These structural changes result in closure of the active site to the bulk solution, which is likely to take place through an induced-fit mechanism, similar to that observed for type I DHNA-CoA synthases. These findings demonstrate that the ligand-dependent conformational changes are a conserved feature of all DHNA-CoA synthases, providing new insights into the catalytic mechanism of this essential tubercular enzyme.

PubMed: 25372686
DOI: 10.1107/S1399004714019440

Experimental method

X-RAY DIFFRACTION (2.2 Å)