8bgr | pdb_00008bgr

FAD-independent Methylene-Tetrahydrofolate Reductase from Mycobacterium hassiacum

spinqualitylabelsall models 8bgr, resolution 1.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8bgr is a 1 chain structure with sequence from Mycolicibacterium hassiacum. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.8Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function K5BDY6_MYCHD Publication Abstract from PubMed FAD-independent methylene-tetrahydrofolate (methylene-H(4) F) reductase (Mfr), recently identified in mycobacteria, catalyzes the reduction of methylene-H(4) F to methyl-H(4) F with NADH as hydride donor by a ternary complex mechanism. This biochemical reaction corresponds to that of the ubiquitous FAD-dependent methylene-H(4) F reductase (MTHFR), although the latter uses a ping-pong mechanism with the prosthetic group as intermediate hydride carrier. Comparative genomics and genetic analyses indicated that Mfr is indispensable for the growth of Mycobacterium tuberculosis, which lacks the MTHFR encoding gene. Therefore, Mfr appears to be an excellent target for the design of antimycobacterial drugs. Here, we report the heterologous production, enzymological characterization, and the crystal structure of Mfr from the thermophilic mycobacterium Mycobacterium hassiacum (hMfr), which shows 78% sequence identity to Mfr from M. tuberculosis. Although hMfr and MTHFR have minor sequence identity and different catalytic mechanisms, their structures are highly similar, thus suggesting a divergent evolution of Mfr and MTHFR from a common ancestor. Most of the important active site residues of MTHFR are conserved and equivalently positioned in the tertiary structure of hMfr. The Glu9Gln variant of hMfr exhibits a drastic reduction of the catalytic activity, which supports the predicted function of the glutamate residue as proton donor in both hMfr and MTHFR. Thus, highly similar binding modes for the C(1) -carriers and the reducing agents in hMfr and MTHFR are assumed. Crystal structure of FAD-independent methylene-tetrahydrofolate reductase from Mycobacterium hassiacum.,Gehl M, Demmer U, Ermler U, Shima S Proteins. 2023 Apr 29. doi: 10.1002/prot.26504. PMID:37119125 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Methylenetetrahydrofolate reductase 3D structures

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