7th5

Thermus thermophilus methylenetetrahydrofolate reductaseThermus thermophilus methylenetetrahydrofolate reductase

Structural highlights 7th5 is a 2 chain structure with sequence from Thermus thermophilus HB8. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.09Å Ligands: , Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function Q5SLG6_THET8 Publication Abstract from PubMed The flavoprotein methylenetetrahydrofolate reductase (MTHFR) catalyzes the reduction of N5, N10-methylenetetrahydrofolate (CH(2)-H(4)folate) to N5-methyltetrahydrofolate (CH(3)-H(4)folate), committing a methyl group from the folate cycle to the methionine one. This committed step is the sum of multiple ping-pong electron transfers involving multiple substrates, intermediates, and products all sharing the same active site. Insight into folate substrate binding is needed to better understand this multifunctional active site. Here, we performed activity assays with Thermus thermophilus MTHFR (tMTHFR), which showed pH-dependent inhibition by the substrate analog, N5-formyltetrahydrofolate (CHO-H(4)folate). Our crystal structure of a tMTHFR*CHO-H(4)folate complex revealed a unique folate-binding mode; tMTHFR subtly rearranges its active site to form a distinct folate binding environment. Formation of a novel binding pocket for the CHO-H(4)folate p-aminobenzoic acid (PABA) moiety directly affects how bent the folate ligand is and its accommodation in the active site. Comparative analysis of the available active (FAD- and folate-bound) MTHFR complex structures reveals that CHO-H(4)folate is accommodated in the active site in a conformation that would not support hydride transfer, but rather in a conformation that potentially reports on a different step in the reaction mechanism after this committed step, such as CH(2)-H(4)folate ring-opening. This active site remodeling provides insights into the functional relevance of the differential folate binding modes and their potential roles in the catalytic cycle. The conformational flexibility displayed by tMTHFR demonstrates how a shared active site can use a few amino acid residues in lieu of extra domains to accommodate chemically-distinct moieties and functionalities. 5-Formyltetrahydrofolate Promotes Conformational Remodeling in a Methylenetetrahydrofolate Reductase Active Site and Inhibits Its Activity.,Yamada K, Mendoza J, Koutmos M J Biol Chem. 2022 Dec 30:102855. doi: 10.1016/j.jbc.2022.102855. PMID:36592927 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Methylenetetrahydrofolate reductase 3D structures

spinqualitylabelsall models 7th5, resolution 2.09Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image