1dhj

<StructureSection load='1dhj' size='340' side='right' caption='[[1dhj]], [[Resolution|resolution]] 1.80&Aring;' scene=''>

<table><tr><td colspan='2'>[[1dhj]] is a 2 chain structure with sequence from [http://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=1DHJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1DHJ FirstGlance]. <br>

</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=MTX:METHOTREXATE'>MTX</scene></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=1dhj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1dhj OCA], [http://pdbe.org/1dhj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1dhj RCSB], [http://www.ebi.ac.uk/pdbsum/1dhj PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1dhj ProSAT]</span></td></tr>

[[http://www.uniprot.org/uniprot/DYR_ECOLI DYR_ECOLI]] Key enzyme in folate metabolism. Catalyzes an essential reaction for de novo glycine and purine synthesis, and for DNA precursor synthesis.

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== Publication Abstract from PubMed ==

X-ray crystal structures have been determined for a second-site revertant (Asp-27--&gt;Ser, Phe-137--&gt;Ser; D27S/F137S) and both component single-site mutants of Escherichia coli dihydrofolate reductase. The primary D27S mutation, located in the substrate binding pocket, greatly reduces catalytic activity as compared to the wild-type enzyme. The additional F137S mutation, which partially restores catalytic activity, is located on the surface of the molecule, well outside of the catalytic center and approximately 15 A from residue 27. Comparison of kinetic data for the single-site F137S mutant, specifically constructed as a control, and for the double-mutant enzymes indicates that the effects of the F137S and D27S mutations on catalysis are nonadditive. This result suggests that the second-site mutation might mediate its effects through a structural perturbation propagated along the polypeptide backbone. To investigate the mechanism by which the F137S substitution elevates the catalytic activity of D27S we have determined the structure of the D27S/F137S double mutant. We also present a rerefined structure for the original D27S mutant and a preliminary structural interpretation for the F137S single-site mutant. We find that while either single mutant shows little more than a simple side-chain substitution, the double mutant undergoes an extended structural perturbation, which is propagated between these two widely separated sites via the helix alpha B.

 

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== References ==

[[Category: Bacillus coli migula 1895]]

[[Category: Dihydrofolate reductase]]

[[Category: Brown, K A]]

[[Category: Kraut, J]]

[[Category: Oxidoreductase]]