4RVG

Crystal structure of MtmC in complex with SAM and TDP

Summary for 4RVG

• Entry DOI: 10.2210/pdb4rvg/pdb
• Related: 1RV9 4RVD 4RVF 4RVH
• Descriptor: D-mycarose 3-C-methyltransferase, ZINC ION, THYMIDINE-5'-DIPHOSPHATE, ... (6 entities in total)
• Functional Keywords: c-methyltransferase, tdp-4-keto-d-olivose, transferase
• Biological source: Streptomyces argillaceus
• Total number of polymer chains: 1
• Total formula weight: 47850.24

Authors

Tsodikov, O.V.,Hou, C.,Chen, J.-M.,Rohr, J. (deposition date: 2014-11-26, release date: 2015-01-28, Last modification date: 2024-02-28)

Primary citation

Chen, J.M.,Hou, C.,Wang, G.,Tsodikov, O.V.,Rohr, J.
Structural Insight into MtmC, a Bifunctional Ketoreductase-Methyltransferase Involved in the Assembly of the Mithramycin Trisaccharide Chain.
Biochemistry, 54:2481-2489, 2015

PubMed Abstract: More and more post-PKS tailoring enzymes are recognized as being multifunctional and codependent on other tailoring enzymes. One of the recently discovered intriguing examples is MtmC, a bifunctional TDP-4-keto-d-olivose ketoreductase-methyltransferase, which-in codependence with glycosyltransferase MtmGIV-is a key contributor to the biosynthesis of the critical trisaccharide chain of the antitumor antibiotic mithramycin (MTM), produced by Streptomyces argillaceus. We report crystal structures of three binary complexes of MtmC with its methylation cosubstrate SAM, its coproduct SAH, and a nucleotide TDP as well as crystal structures of two ternary complexes, MtmC-SAH-TDP-4-keto-d-olivose and MtmC-SAM-TDP, in the range of 2.2-2.7 Å resolution. The structures reveal general and sugar-specific recognition and catalytic structural features of MtmC. Depending on the catalytic function that is conducted by MtmC, it must bind either NADPH or SAM in the same cofactor binding pocket. A tyrosine residue (Tyr79) appears as a lid covering the sugar moiety of the substrate during the methyl transfer reaction. This residue swings out of the active site by ~180° in the absence of the substrate. This unique conformational change likely serves to release the methylated product and, possibly, to open the active site for binding the bulkier cosubstrate NADPH prior to the reduction reaction.

PubMed: 25587924
DOI: 10.1021/bi501462g

Experimental method

X-RAY DIFFRACTION (2.3 Å)