9I32
Alpha-Methylacyl-CoA racemase from Mycobacterium tuberculosis in complex with isobutanoyl-CoA
Summary for 9I32
| Entry DOI | 10.2210/pdb9i32/pdb |
| Descriptor | Alpha-methylacyl-CoA racemase, ISOBUTYRYL-COENZYME A (3 entities in total) |
| Functional Keywords | coa-transferase, epimerization, coa-transferase family iii, alpha proton exchange, homo dimer, isomerase, isobutanoyl-coa, isobutanol |
| Biological source | Mycobacterium tuberculosis |
| Total number of polymer chains | 12 |
| Total formula weight | 478376.99 |
| Authors | |
| Primary citation | Mojanaga, O.O.,Woodman, T.J.,Lloyd, M.D.,Acharya, K.R. Molecular basis of acyl-CoA ester recognition by alpha-methylacyl-CoA racemase from Mycobacterium tuberculosis. J.Biol.Chem., :110302-110302, 2025 Cited by PubMed Abstract: α-Methylacyl-CoA racemase (AMACR; P504S) enzyme plays a vital role in branched-chain fatty acid metabolism by catalysing the conversion of 2-methyl-branched fatty acyl-CoAs into a near 1 to 1 mixture of the (2R)- and (2S)-epimers, enabling further metabolism. α-Methylacyl-CoA racemase from Mycobacterium tuberculosis (MCR) has been explored as a model to understand the AMACR racemization mechanism and as a drug target. Here we present a detailed analysis of a new MCR wild-type crystal structure to provide insights into the MCR racemization mechanism and the molecular features that contribute enzyme activity and selectivity. Specifically, we report a structure of wild-type MCR (in tetragonal space group I422, a new crystal form) along with 12 structures of MCR in complex with branched-chain 2-methylacyl-CoA esters (ibuprofenoyl-CoA, ±-fenoprofenoyl-CoA, S-ketoprofenoyl-CoA, ±-flurbiprofenoyl-CoA, S-naproxenoyl-CoA, S-2-methyldecanoyl-CoA, and isobutanoyl-CoA) and straight-chain acyl-CoA esters (decanoyl-CoA, octanoyl-CoA, hexanoyl-CoA, butanoyl-CoA, acetyl-CoA) in the range of 1.88 to 2.40 Å resolution. These detailed molecular structures enhance our understanding of substrate recognition and coupled with extensive enzyme inhibition assays provide a framework for the rational structure-based drug design of selective and potent MCR inhibitors to combat Mycobacterium tuberculosis in the future. PubMed: 40447188DOI: 10.1016/j.jbc.2025.110302 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.94 Å) |
Structure validation
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