2lf1: Difference between revisions
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<StructureSection load='2lf1' size='340' side='right' caption='[[2lf1]], [[NMR_Ensembles_of_Models | 30 NMR models]]' scene=''> | <StructureSection load='2lf1' size='340' side='right' caption='[[2lf1]], [[NMR_Ensembles_of_Models | 30 NMR models]]' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[2lf1]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/ | <table><tr><td colspan='2'>[[2lf1]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_a"_von_freudenreich_1890 "bacillus a" von freudenreich 1890]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2LF1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2LF1 FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2l28|2l28]], [[1lud|1lud]], [[2hm9|2hm9]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2l28|2l28]], [[1lud|1lud]], [[2hm9|2hm9]]</td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">folA, dhfR ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1582 | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">folA, dhfR ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1582 "Bacillus a" von Freudenreich 1890])</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='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=2lf1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2lf1 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2lf1 RCSB], [http://www.ebi.ac.uk/pdbsum/2lf1 PDBsum]</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=2lf1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2lf1 OCA], [http://pdbe.org/2lf1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2lf1 RCSB], [http://www.ebi.ac.uk/pdbsum/2lf1 PDBsum]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | </div> | ||
<div class="pdbe-citations 2lf1" style="background-color:#fffaf0;"></div> | |||
==See Also== | ==See Also== | ||
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__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Bacillus a von freudenreich 1890]] | |||
[[Category: Dihydrofolate reductase]] | [[Category: Dihydrofolate reductase]] | ||
[[Category: Birdsall, B]] | [[Category: Birdsall, B]] | ||
[[Category: Feeney, J]] | [[Category: Feeney, J]] | ||
Revision as of 17:24, 11 September 2015
Solution structure of L. casei dihydrofolate reductase complexed with NADPH, 30 structuresSolution structure of L. casei dihydrofolate reductase complexed with NADPH, 30 structures
Structural highlights
Function[DYR_LACCA] Key enzyme in folate metabolism. Catalyzes an essential reaction for de novo glycine and purine synthesis, and for DNA precursor synthesis. Publication Abstract from PubMedIn order to examine the origins of the large positive cooperativity (Gcoop = -2.9 kcal mol-1) of trimethoprim (TMP) binding to a bacterial dihydrofolate reductase (DHFR) in the presence of NADPH we have determined and compared NMR solution structures of L. casei apo DHFR and its binary and ternary complexes with TMP and NADPH, and made complementary thermodynamic measurements. The DHFR structures are generally very similar except for the A-B loop region and part of helix B (residues 15-31) which could not be directly detected for L. casei apo DHFR because of line-broadening from exchange between folded and unfolded forms. Thermodynamic and NMR measurements suggested that a significant but not dominant contribution to the cooperativity comes from refolding of apo DHFR on binding the first ligand (up to -0.7 kcals mol-1 estimated for A-B loop refolding). Comparisons of C-C distance differences and domain rotation angles between apo DHFR and its complexes indicated that generally similar conformational changes involving domain movements accompany formation of the binary complexes with either TMP or NADPH, and that the binary structures are approaching that of the ternary complex as would be expected for positive cooperativity. These favorable ligand-induced structural changes upon binding the first ligand will also contribute significantly to the cooperative binding. A further substantial contribution to cooperative binding results from the proximity of the bound ligands in the ternary complex: this reduces the solvent accessible area of the ligand and provides a favorable entropic hydrophobic contribution (up to -1.4 kcal mol-1). NMR structures of apo L.casei dihydrofolate reductase and its complexes with trimethoprim and NADPH. Contributions to positive cooperative binding from ligand-induced refolding, conformational changes and interligand hydrophobic interactionsdagger.,Feeney J, Birdsall B, Kovalevskaya NV, Smurnyy YD, Navarro-Peran EM, Polshakov VI Biochemistry. 2011 Mar 16. PMID:21410224[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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