View source for 7wmw


==Crystal structure of methylenetetrahydrofolate reductase MSMEG_6649 from Mycobacterium smegmatis==
<StructureSection load='7wmw' size='340' side='right'caption='[[7wmw]], [[Resolution|resolution]] 2.05&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7wmw]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycolicibacterium_smegmatis_MC2_155 Mycolicibacterium smegmatis MC2 155]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7WMW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7WMW FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.053&#8491;</td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7wmw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7wmw OCA], [https://pdbe.org/7wmw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7wmw RCSB], [https://www.ebi.ac.uk/pdbsum/7wmw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7wmw ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/A0R6S0_MYCS2 A0R6S0_MYCS2] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
5,10-Methylenetetraydrofolate reductase (MTHFR) is a key enzyme in folate metabolism. MSMEG_6649, a non-canonical MTHFR from Mycobacterium smegmatis, was previously reported as a monomeric protein lacking the flavin coenzyme. However, the structural basis for its unique flavin-independent catalytic mechanism remains poorly understood. Here, we determined the crystal structures of apo MTHFR MSMEG_6649 and its complex with NADH from M. smegmatis. Structural analysis revealed that the groove formed by the loops 4 and 5 of non-canonical MSMEG_6649 interacting with FAD was significantly larger than that of canonical MTHFR. Meanwhile, the NADH-binding site in MSMEG_6649 is highly similar to the FAD binding site in canonical MTHFR, suggesting that NADH plays the same role (immediate hydride donor for methylenetetraydrofolate) as FAD in the catalytic reaction. Using biochemical analysis, molecular modeling, and site-directed mutagenesis, the critical residues participating in the binding of NADH and the substrate 5,10-methylenetetrahydrofolate as well as the product 5-methyltetrahydrofolate were identified and validated. Taken together, this work not only provides a good starting point for understanding the potential catalytic mechanism for MSMEG_6649, but also identifies an exploitable target for the development of anti-mycobacterial drugs.

Structural and functional characterization of a mycobacterial methylenetetrahydrofolate reductase utilizing NADH as the exclusive cofactor.,Li J, Yang M, Li W, Lu C, Feng D, Shang Z, Wang C, Lin W Biochem J. 2023 Jul 26;480(14):1129-1146. doi: 10.1042/BCJ20230138. PMID:37435857<ref>PMID:37435857</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7wmw" style="background-color:#fffaf0;"></div>

==See Also==
*[[Methylenetetrahydrofolate reductase 3D structures|Methylenetetrahydrofolate reductase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Mycolicibacterium smegmatis MC2 155]]
[[Category: Lin W]]
[[Category: Wang W]]