6mt8: Difference between revisions
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<StructureSection load='6mt8' size='340' side='right'caption='[[6mt8]], [[Resolution|resolution]] 1.35Å' scene=''> | <StructureSection load='6mt8' size='340' side='right'caption='[[6mt8]], [[Resolution|resolution]] 1.35Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[6mt8]] is a 1 chain structure with sequence from [ | <table><tr><td colspan='2'>[[6mt8]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli_K-12 Escherichia coli K-12]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6MT8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6MT8 FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=DHF:DIHYDROFOLIC+ACID'>DHF</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=THG:(6S)-5,6,7,8-TETRAHYDROFOLATE'>THG</scene | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.35Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=DHF:DIHYDROFOLIC+ACID'>DHF</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=THG:(6S)-5,6,7,8-TETRAHYDROFOLATE'>THG</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=6mt8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6mt8 OCA], [https://pdbe.org/6mt8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6mt8 RCSB], [https://www.ebi.ac.uk/pdbsum/6mt8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6mt8 ProSAT]</span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | |||
</table> | </table> | ||
== Function == | == Function == | ||
[ | [https://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. | ||
<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: | [[Category: Escherichia coli K-12]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Benach | [[Category: Benach J]] | ||
[[Category: Cao | [[Category: Cao H]] | ||
[[Category: Frommelt | [[Category: Frommelt A]] | ||
[[Category: Koss | [[Category: Koss J]] | ||
[[Category: Morisco | [[Category: Morisco L]] | ||
[[Category: Rodrigues | [[Category: Rodrigues J]] | ||
[[Category: Shakhnovich | [[Category: Shakhnovich E]] | ||
[[Category: Skolnick | [[Category: Skolnick J]] | ||
Latest revision as of 09:38, 11 October 2023
E. coli DHFR complex modeled with two ligand statesE. coli DHFR complex modeled with two ligand states
Structural highlights
FunctionDYR_ECOLI Key enzyme in folate metabolism. Catalyzes an essential reaction for de novo glycine and purine synthesis, and for DNA precursor synthesis. Publication Abstract from PubMedTime-resolved crystallography is a powerful technique to elucidate molecular mechanisms at both spatial (angstroms) and temporal (picoseconds to seconds) resolutions. We recently discovered an unusually slow reaction at room temperature that occurs on the order of days: the in crystalline reverse oxidative decay of the chemically labile (6S)-5,6,7,8-tetrahydrofolate in complex with its producing enzyme Escherichia coli dihydrofolate reductase. Here, we report the critical analysis of a representative dataset at an intermediate reaction time point. A quinonoid-like intermediate state lying between tetrahydrofolate and dihydrofolate features a near coplanar geometry of the bicyclic pterin moiety, and a tetrahedral sp (3) C6 geometry is proposed based on the apparent mFo-DFc omit electron densities of the ligand. The presence of this intermediate is strongly supported by Bayesian difference refinement. Isomorphous Fo-Fo difference map and multi-state refinement analyses suggest the presence of end-state ligand populations as well, although the putative intermediate state is likely the most populated. A similar quinonoid intermediate previously proposed to transiently exist during the oxidation of tetrahydrofolate was confirmed by polarography and UV-vis spectroscopy to be relatively stable in the oxidation of its close analog tetrahydropterin. We postulate that the constraints on the ligand imposed by the interactions with the protein environment might be the origin of the slow reaction observed by time-resolved crystallography. Time-resolved x-ray crystallography capture of a slow reaction tetrahydrofolate intermediate.,Cao H, Skolnick J Struct Dyn. 2019 Mar 1;6(2):024701. doi: 10.1063/1.5086436. eCollection 2019 Mar. PMID:30868089[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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