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| | <StructureSection load='4rgc' size='340' side='right'caption='[[4rgc]], [[Resolution|resolution]] 1.05Å' scene=''> | | <StructureSection load='4rgc' size='340' side='right'caption='[[4rgc]], [[Resolution|resolution]] 1.05Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4rgc]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Escherichia_coli_str._k-12_substr._mc4100 Escherichia coli str. k-12 substr. mc4100]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=4psz 4psz]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4RGC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4RGC FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4rgc]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli_str._K-12_substr._MC4100 Escherichia coli str. K-12 substr. MC4100]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=4psz 4psz]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4RGC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4RGC FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FOL:FOLIC+ACID'>FOL</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CSD:3-SULFINOALANINE'>CSD</scene>, <scene name='pdbligand=FOL:FOLIC+ACID'>FOL</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene></td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CSD:3-SULFINOALANINE'>CSD</scene></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=4rgc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4rgc OCA], [https://pdbe.org/4rgc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4rgc RCSB], [https://www.ebi.ac.uk/pdbsum/4rgc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4rgc ProSAT]</span></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4psy|4psy]], [[4pst|4pst]], [[4ptj|4ptj]]</td></tr>
| + | |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">BN896_0046, folA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1403831 Escherichia coli str. K-12 substr. MC4100])</td></tr>
| + | |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Dihydrofolate_reductase Dihydrofolate reductase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.5.1.3 1.5.1.3] </span></td></tr>
| + | |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4rgc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4rgc OCA], [http://pdbe.org/4rgc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4rgc RCSB], [http://www.ebi.ac.uk/pdbsum/4rgc PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4rgc ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| - | == Function == | |
| - | [[http://www.uniprot.org/uniprot/U6N356_ECOLI U6N356_ECOLI]] Key enzyme in folate metabolism. Catalyzes an essential reaction for de novo glycine and purine synthesis, and for DNA precursor synthesis (By similarity).[PIRNR:PIRNR000194] | |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | | | |
| | ==See Also== | | ==See Also== |
| - | *[[Dihydrofolate reductase|Dihydrofolate reductase]] | + | *[[Dihydrofolate reductase 3D structures|Dihydrofolate reductase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Dihydrofolate reductase]]
| + | [[Category: Escherichia coli str. K-12 substr. MC4100]] |
| - | [[Category: Escherichia coli str. k-12 substr. mc4100]] | + | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Bennett, B C]] | + | [[Category: Bennett BC]] |
| - | [[Category: Dealwis, C]] | + | [[Category: Dealwis C]] |
| - | [[Category: Wan, Q]] | + | [[Category: Wan Q]] |
| - | [[Category: Wilson, M A]] | + | [[Category: Wilson MA]] |
| - | [[Category: Oxidoreductase]]
| + | |
| - | [[Category: Reductase]]
| + | |
| Structural highlights
Publication Abstract from PubMed
Dihydrofolate reductase (DHFR) catalyzes the NADPH-dependent reduction of dihydrofolate (DHF) to tetrahydrofolate (THF). An important step in the mechanism involves proton donation to the N5 atom of DHF. The inability to determine the protonation states of active site residues and substrate has led to a lack of consensus regarding the catalytic mechanism involved. To resolve this ambiguity, we conducted neutron and ultrahigh-resolution X-ray crystallographic studies of the pseudo-Michaelis ternary complex of Escherichia coli DHFR with folate and NADP+. The neutron data were collected to 2.0-A resolution using a 3.6-mm3 crystal with the quasi-Laue technique. The structure reveals that the N3 atom of folate is protonated, whereas Asp27 is negatively charged. Previous mechanisms have proposed a keto-to-enol tautomerization of the substrate to facilitate protonation of the N5 atom. The structure supports the existence of the keto tautomer owing to protonation of the N3 atom, suggesting that tautomerization is unnecessary for catalysis. In the 1.05-A resolution X-ray structure of the ternary complex, conformational disorder of the Met20 side chain is coupled to electron density for a partially occupied water within hydrogen-bonding distance of the N5 atom of folate; this suggests direct protonation of substrate by solvent. We propose a catalytic mechanism for DHFR that involves stabilization of the keto tautomer of the substrate, elevation of the pKa value of the N5 atom of DHF by Asp27, and protonation of N5 by water that gains access to the active site through fluctuation of the Met20 side chain even though the Met20 loop is closed.
Toward resolving the catalytic mechanism of dihydrofolate reductase using neutron and ultrahigh-resolution X-ray crystallography.,Wan Q, Bennett BC, Wilson MA, Kovalevsky A, Langan P, Howell EE, Dealwis C Proc Natl Acad Sci U S A. 2014 Dec 1. pii: 201415856. PMID:25453083[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Wan Q, Bennett BC, Wilson MA, Kovalevsky A, Langan P, Howell EE, Dealwis C. Toward resolving the catalytic mechanism of dihydrofolate reductase using neutron and ultrahigh-resolution X-ray crystallography. Proc Natl Acad Sci U S A. 2014 Dec 1. pii: 201415856. PMID:25453083 doi:http://dx.doi.org/10.1073/pnas.1415856111
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