View source for 7fq5


==DHFR:NADP+:FOL complex at 310 K (crystal 3)==
<StructureSection load='7fq5' size='340' side='right'caption='[[7fq5]], [[Resolution|resolution]] 1.35&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7fq5]] 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=7FQ5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7FQ5 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.35&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CSD:3-SULFINOALANINE'>CSD</scene>, <scene name='pdbligand=FOL:FOLIC+ACID'>FOL</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</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=7fq5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7fq5 OCA], [https://pdbe.org/7fq5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7fq5 RCSB], [https://www.ebi.ac.uk/pdbsum/7fq5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7fq5 ProSAT]</span></td></tr>
</table>
== 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;">
== Publication Abstract from PubMed ==
Enzymes catalyze biochemical reactions through precise positioning of substrates, cofactors, and amino acids to modulate the transition-state free energy. However, the role of conformational dynamics remains poorly understood due to poor experimental access. This shortcoming is evident with Escherichia coli dihydrofolate reductase (DHFR), a model system for the role of protein dynamics in catalysis, for which it is unknown how the enzyme regulates the different active site environments required to facilitate proton and hydride transfer. Here, we describe ligand-, temperature-, and electric-field-based perturbations during X-ray diffraction experiments to map the conformational dynamics of the Michaelis complex of DHFR. We resolve coupled global and local motions and find that these motions are engaged by the protonated substrate to promote efficient catalysis. This result suggests a fundamental design principle for multistep enzymes in which pre-existing dynamics enable intermediates to drive rapid electrostatic reorganization to facilitate subsequent chemical steps.

Perturbative diffraction methods resolve a conformational switch that facilitates a two-step enzymatic mechanism.,Greisman JB, Dalton KM, Brookner DE, Klureza MA, Sheehan CJ, Kim IS, Henning RW, Russi S, Hekstra DR Proc Natl Acad Sci U S A. 2024 Feb 27;121(9):e2313192121. doi: , 10.1073/pnas.2313192121. Epub 2024 Feb 22. PMID:38386706<ref>PMID:38386706</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7fq5" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Escherichia coli K-12]]
[[Category: Large Structures]]
[[Category: Brookner DE]]
[[Category: Dalton KM]]
[[Category: Greisman JB]]
[[Category: Hekstra DR]]