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| | <StructureSection load='4qlf' size='340' side='right'caption='[[4qlf]], [[Resolution|resolution]] 1.44Å' scene=''> | | <StructureSection load='4qlf' size='340' side='right'caption='[[4qlf]], [[Resolution|resolution]] 1.44Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4qlf]] 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]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4QLF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4QLF FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4qlf]] 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]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4QLF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4QLF 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=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=FOL:FOLIC+ACID'>FOL</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4qle|4qle]], [[4qlg|4qlg]]</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=4qlf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qlf OCA], [https://pdbe.org/4qlf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4qlf RCSB], [https://www.ebi.ac.uk/pdbsum/4qlf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4qlf ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">folA, BN896_0046 ([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=4qlf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qlf OCA], [http://pdbe.org/4qlf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4qlf RCSB], [http://www.ebi.ac.uk/pdbsum/4qlf PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4qlf 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: Gakhar, L]] | + | [[Category: Gakhar L]] |
| - | [[Category: Kohen, A]] | + | [[Category: Kohen A]] |
| - | [[Category: Stojkovic, V]] | + | [[Category: Stojkovic V]] |
| - | [[Category: Oxidoreductase]]
| + | |
| - | [[Category: Oxidoreductase activity]]
| + | |
| Structural highlights
Publication Abstract from PubMed
This study employs hybrid quantum mechanics-molecular mechanics (QM/MM) simulations to investigate the effect of mutations of the active-site residue I14 of E. coli dihydrofolate reductase (DHFR) on the hydride transfer. Recent kinetic measurements of the I14X mutants (X = V, A, and G) indicated slower hydride transfer rates and increasingly temperature-dependent kinetic isotope effects (KIEs) with systematic reduction of the I14 side chain. The QM/MM simulations show that when the original isoleucine residue is substituted in silico by valine, alanine, or glycine (I14V, I14A, and I14G DHFR, respectively), the free energy barrier height of the hydride transfer reaction increases relative to the wild-type enzyme. These trends are in line with the single-turnover rate measurements reported for these systems. In addition, extended dynamics simulations of the reactive Michaelis complex reveal enhanced flexibility in the mutants, and in particular for the I14G mutant, including considerable fluctuations of the donor-acceptor distance (DAD) and the active-site hydrogen bonding network compared with those detected in the native enzyme. These observations suggest that the perturbations induced by the mutations partly impair the active-site environment in the reactant state. On the other hand, the average DADs at the transition state of all DHFR variants are similar. Crystal structures of I14 mutants (V, A, and G) confirmed the trend of increased flexibility of the M20 and other loops.
Free Energy Simulations of Active-Site Mutants of Dihydrofolate Reductase.,Doron D, Stojkovic V, Gakhar L, Vardi-Kilshtain A, Kohen A, Major DT J Phys Chem B. 2014 Nov 21. PMID:25382260[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Doron D, Stojkovic V, Gakhar L, Vardi-Kilshtain A, Kohen A, Major DT. Free Energy Simulations of Active-Site Mutants of Dihydrofolate Reductase. J Phys Chem B. 2014 Nov 21. PMID:25382260 doi:http://dx.doi.org/10.1021/jp5059963
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