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| | <StructureSection load='1zrq' size='340' side='right'caption='[[1zrq]], [[Resolution|resolution]] 2.20Å' scene=''> | | <StructureSection load='1zrq' size='340' side='right'caption='[[1zrq]], [[Resolution|resolution]] 2.20Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1zrq]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/"bacillus_coli"_migula_1895 "bacillus coli" migula 1895]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ZRQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1ZRQ FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1zrq]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ZRQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1ZRQ FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=NAI:1,4-DIHYDRONICOTINAMIDE+ADENINE+DINUCLEOTIDE'>NAI</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.2Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1b5t|1b5t]], [[1zp3|1zp3]], [[1zp4|1zp4]], [[1zpt|1zpt]]</div></td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=NAI:1,4-DIHYDRONICOTINAMIDE+ADENINE+DINUCLEOTIDE'>NAI</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">metF ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=562 "Bacillus coli" Migula 1895])</td></tr> | + | |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Methylenetetrahydrofolate_reductase_(NAD(P)H) Methylenetetrahydrofolate reductase (NAD(P)H)], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.5.1.20 1.5.1.20] </span></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=1zrq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1zrq OCA], [https://pdbe.org/1zrq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1zrq RCSB], [https://www.ebi.ac.uk/pdbsum/1zrq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1zrq ProSAT]</span></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=1zrq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1zrq OCA], [https://pdbe.org/1zrq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1zrq RCSB], [https://www.ebi.ac.uk/pdbsum/1zrq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1zrq ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/METF_ECOLI METF_ECOLI]] Methylenetetrahydrofolate reductase required to generate the methyl groups necessary for methionine synthetase to convert homocysteine to methionine.<ref>PMID:14275142</ref>
| + | [https://www.uniprot.org/uniprot/METF_ECOLI METF_ECOLI] Methylenetetrahydrofolate reductase required to generate the methyl groups necessary for methionine synthetase to convert homocysteine to methionine.<ref>PMID:14275142</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | </div> | | </div> |
| | <div class="pdbe-citations 1zrq" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 1zrq" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Methylenetetrahydrofolate reductase 3D structures|Methylenetetrahydrofolate reductase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Bacillus coli migula 1895]] | + | [[Category: Escherichia coli]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Ludwig, M L]] | + | [[Category: Ludwig ML]] |
| - | [[Category: Pejchal, R]] | + | [[Category: Pejchal R]] |
| - | [[Category: Sargeant, R]] | + | [[Category: Sargeant R]] |
| - | [[Category: Flavin]]
| + | |
| - | [[Category: Nadh]]
| + | |
| - | [[Category: Oxidoreductase]]
| + | |
| - | [[Category: Reductase]]
| + | |
| - | [[Category: Tim barrel]]
| + | |
| Structural highlights
Function
METF_ECOLI Methylenetetrahydrofolate reductase required to generate the methyl groups necessary for methionine synthetase to convert homocysteine to methionine.[1]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Methylenetetrahydrofolate reductases (MTHFRs; EC 1.7.99.5) catalyze the NAD(P)H-dependent reduction of 5,10-methylenetetrahydrofolate (CH(2)-H(4)folate) to 5-methyltetrahydrofolate (CH(3)-H(4)folate) using flavin adenine dinucleotide (FAD) as a cofactor. The initial X-ray structure of Escherichia coli MTHFR revealed that this 33-kDa polypeptide is a (betaalpha)(8) barrel that aggregates to form an unusual tetramer with only 2-fold symmetry. Structures of reduced enzyme complexed with NADH and of oxidized Glu28Gln enzyme complexed with CH(3)-H(4)folate have now been determined at resolutions of 1.95 and 1.85 A, respectively. The NADH complex reveals a rare mode of dinucleotide binding; NADH adopts a hairpin conformation and is sandwiched between a conserved phenylalanine, Phe223, and the isoalloxazine ring of FAD. The nicotinamide of the bound pyridine nucleotide is stacked against the si face of the flavin ring with C4 adjoining the N5 of FAD, implying that this structure models a complex that is competent for hydride transfer. In the complex with CH(3)-H(4)folate, the pterin ring is also stacked against FAD in an orientation that is favorable for hydride transfer. Thus, the binding sites for the two substrates overlap, as expected for many enzymes that catalyze ping-pong reactions, and several invariant residues interact with both folate and pyridine nucleotide substrates. Comparisons of liganded and substrate-free structures reveal multiple conformations for the loops beta2-alpha2 (L2), beta3-alpha3 (L3), and beta4-alpha4 (L4) and suggest that motions of these loops facilitate the ping-pong reaction. In particular, the L4 loop adopts a "closed" conformation that allows Asp120 to hydrogen bond to the pterin ring in the folate complex but must move to an "open" conformation to allow NADH to bind.
Structures of NADH and CH3-H4folate complexes of Escherichia coli methylenetetrahydrofolate reductase reveal a spartan strategy for a ping-pong reaction.,Pejchal R, Sargeant R, Ludwig ML Biochemistry. 2005 Aug 30;44(34):11447-57. PMID:16114881[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ KATZEN HM, BUCHANAN JM. ENZYMATIC SYNTHESIS OF THE METHYL GROUP OF METHIONINE. 8. REPRESSION-DEREPRESSION, PURIFICATION, AND PROPERTIES OF 5,10-METHYLENETETRAHYDROFOLATE REDUCTASE FROM ESCHERICHIA COLI. J Biol Chem. 1965 Feb;240:825-35. PMID:14275142
- ↑ Pejchal R, Sargeant R, Ludwig ML. Structures of NADH and CH3-H4folate complexes of Escherichia coli methylenetetrahydrofolate reductase reveal a spartan strategy for a ping-pong reaction. Biochemistry. 2005 Aug 30;44(34):11447-57. PMID:16114881 doi:10.1021/bi050533q
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