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| | ==Solution structure of lactobacillus casei dihydrofolate reductase apo-form, 25 conformers== | | ==Solution structure of lactobacillus casei dihydrofolate reductase apo-form, 25 conformers== |
| - | <StructureSection load='2l28' size='340' side='right'caption='[[2l28]], [[NMR_Ensembles_of_Models | 25 NMR models]]' scene=''> | + | <StructureSection load='2l28' size='340' side='right'caption='[[2l28]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2l28]] is a 1 chain structure with sequence from [https://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=2L28 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2L28 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2l28]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Lacticaseibacillus_casei Lacticaseibacillus casei]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2L28 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2L28 FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1lud|1lud]], [[2hm9|2hm9]], [[2hqp|2hqp]], [[1yho|1yho]]</div></td></tr> | + | </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=2l28 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2l28 OCA], [https://pdbe.org/2l28 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2l28 RCSB], [https://www.ebi.ac.uk/pdbsum/2l28 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2l28 ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">folA, dhfR ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1582 "Bacillus a" von Freudenreich 1890])</td></tr>
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| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Dihydrofolate_reductase Dihydrofolate reductase], with EC number [https://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'>[https://proteopedia.org/fgij/fg.htm?mol=2l28 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2l28 OCA], [https://pdbe.org/2l28 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2l28 RCSB], [https://www.ebi.ac.uk/pdbsum/2l28 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2l28 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/DYR_LACCA DYR_LACCA]] Key enzyme in folate metabolism. Catalyzes an essential reaction for de novo glycine and purine synthesis, and for DNA precursor synthesis.
| + | [https://www.uniprot.org/uniprot/DYR_LACCA DYR_LACCA] Key enzyme in folate metabolism. Catalyzes an essential reaction for de novo glycine and purine synthesis, and for DNA precursor synthesis. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Bacillus a von freudenreich 1890]] | + | [[Category: Lacticaseibacillus casei]] |
| - | [[Category: Dihydrofolate reductase]]
| + | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Birdsall, B]] | + | [[Category: Birdsall B]] |
| - | [[Category: Feeney, J]] | + | [[Category: Feeney J]] |
| - | [[Category: Polshakov, V I]] | + | [[Category: Polshakov VI]] |
| - | [[Category: Antifolate]]
| + | |
| - | [[Category: Co-operative binding]]
| + | |
| - | [[Category: Dhfr]]
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| - | [[Category: Oxidoreductase]]
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| 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 PubMed
In 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 Also
References
- ↑ Feeney J, Birdsall B, Kovalevskaya NV, Smurnyy YD, Navarro-Peran EM, Polshakov VI. 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. Biochemistry. 2011 Mar 16. PMID:21410224 doi:10.1021/bi200067t
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