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Crystal structure of UDP-N-acetylglucosamine-enolpyruvate reductase (MurB) from Mycobacterium tuberculosis.
Biochim Biophys Acta Proteins Proteom. 2018 Mar; 1866(3):397-406.BB

Abstract

The biosynthesis of UDP-N-acetylmuramic acid (UDP-MurNAc) by reduction of UDP-N-acetylglucosamine-enolpyruvate (UDP-GlcNAc-EP) in an NADPH and FAD-dependent reaction in bacteria is one of the key steps in peptidoglycan biosynthesis catalyzed by UDP-N-acetylglucosamine-enolpyruvate reductase (MurB). Here, we present the crystal structure of Mycobacterium tuberculosis MurB (MtbMurB) with FAD as the prosthetic group at 2.0Å resolution. There are six molecules in asymmetric unit in the form of dimers. Each protomer can be subdivided into three domains and the prosthetic group, FAD is bound in the active site between domain I and domain II. Comparison of MtbMurB structure with the structures of the Escherichia coli MurB (in complex with UDP-GlcNAc-EP) and Pseudomonas aeruginosa MurB (in complex with NADPH) showed all three structures share similar domain architecture and residues in the active site. The nicotinamide and the enol pyruvyl moieties are well aligned upon superimposition, both positioned in suitable position for hydride transfer to and from FAD. The comparison studies and MD simulations demonstrate that the two lobes of domain-III become more flexible. The substrates (NADPH and UDP-GlcNAc-EP) binding responsible for open conformation of MurB, suggesting that NADPH and UDP-GlcNAc-EP interactions are conformationally stable. Our findings provide a detail mechanism about the closed to open state by binding of NADPH and UDP-GlcNAc-EP induces the conformational changes of MurB structure that may trigger the MurB catalytic reaction.

Authors+Show Affiliations

Department of Biomedical Science, Acharya Narendra Dev College, University of Delhi, New Delhi, India.School of Life Sciences, Jawaharlal Nehru University, New Delhi, India.School of Life Sciences, Jawaharlal Nehru University, New Delhi, India.Department of Biomedical Science, Acharya Narendra Dev College, University of Delhi, New Delhi, India. Electronic address: urmibajpai@andc.du.ac.in.School of Life Sciences, Jawaharlal Nehru University, New Delhi, India. Electronic address: sgourinath@mail.jnu.ac.in.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

29203374

Citation

Eniyan, Kandasamy, et al. "Crystal Structure of UDP-N-acetylglucosamine-enolpyruvate Reductase (MurB) From Mycobacterium Tuberculosis." Biochimica Et Biophysica Acta. Proteins and Proteomics, vol. 1866, no. 3, 2018, pp. 397-406.
Eniyan K, Dharavath S, Vijayan R, et al. Crystal structure of UDP-N-acetylglucosamine-enolpyruvate reductase (MurB) from Mycobacterium tuberculosis. Biochim Biophys Acta Proteins Proteom. 2018;1866(3):397-406.
Eniyan, K., Dharavath, S., Vijayan, R., Bajpai, U., & Gourinath, S. (2018). Crystal structure of UDP-N-acetylglucosamine-enolpyruvate reductase (MurB) from Mycobacterium tuberculosis. Biochimica Et Biophysica Acta. Proteins and Proteomics, 1866(3), 397-406. https://doi.org/10.1016/j.bbapap.2017.11.013
Eniyan K, et al. Crystal Structure of UDP-N-acetylglucosamine-enolpyruvate Reductase (MurB) From Mycobacterium Tuberculosis. Biochim Biophys Acta Proteins Proteom. 2018;1866(3):397-406. PubMed PMID: 29203374.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Crystal structure of UDP-N-acetylglucosamine-enolpyruvate reductase (MurB) from Mycobacterium tuberculosis. AU - Eniyan,Kandasamy, AU - Dharavath,Sudhaker, AU - Vijayan,Ramachandran, AU - Bajpai,Urmi, AU - Gourinath,Samudrala, Y1 - 2017/12/05/ PY - 2017/06/23/received PY - 2017/11/23/revised PY - 2017/11/28/accepted PY - 2017/12/6/pubmed PY - 2018/5/11/medline PY - 2017/12/6/entrez KW - FAD KW - Mycobacterium tuberculosis KW - NADPH KW - UDP-GlcNAc-EP KW - UDP-MurNAc SP - 397 EP - 406 JF - Biochimica et biophysica acta. Proteins and proteomics JO - Biochim Biophys Acta Proteins Proteom VL - 1866 IS - 3 N2 - The biosynthesis of UDP-N-acetylmuramic acid (UDP-MurNAc) by reduction of UDP-N-acetylglucosamine-enolpyruvate (UDP-GlcNAc-EP) in an NADPH and FAD-dependent reaction in bacteria is one of the key steps in peptidoglycan biosynthesis catalyzed by UDP-N-acetylglucosamine-enolpyruvate reductase (MurB). Here, we present the crystal structure of Mycobacterium tuberculosis MurB (MtbMurB) with FAD as the prosthetic group at 2.0Å resolution. There are six molecules in asymmetric unit in the form of dimers. Each protomer can be subdivided into three domains and the prosthetic group, FAD is bound in the active site between domain I and domain II. Comparison of MtbMurB structure with the structures of the Escherichia coli MurB (in complex with UDP-GlcNAc-EP) and Pseudomonas aeruginosa MurB (in complex with NADPH) showed all three structures share similar domain architecture and residues in the active site. The nicotinamide and the enol pyruvyl moieties are well aligned upon superimposition, both positioned in suitable position for hydride transfer to and from FAD. The comparison studies and MD simulations demonstrate that the two lobes of domain-III become more flexible. The substrates (NADPH and UDP-GlcNAc-EP) binding responsible for open conformation of MurB, suggesting that NADPH and UDP-GlcNAc-EP interactions are conformationally stable. Our findings provide a detail mechanism about the closed to open state by binding of NADPH and UDP-GlcNAc-EP induces the conformational changes of MurB structure that may trigger the MurB catalytic reaction. SN - 1570-9639 UR - https://www.unboundmedicine.com/medline/citation/29203374/Crystal_structure_of_UDP_N_acetylglucosamine_enolpyruvate_reductase__MurB__from_Mycobacterium_tuberculosis_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1570-9639(17)30281-9 DB - PRIME DP - Unbound Medicine ER -