6vim: Difference between revisions
No edit summary |
No edit summary |
||
| Line 3: | Line 3: | ||
<StructureSection load='6vim' size='340' side='right'caption='[[6vim]], [[Resolution|resolution]] 2.00Å' scene=''> | <StructureSection load='6vim' size='340' side='right'caption='[[6vim]], [[Resolution|resolution]] 2.00Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[6vim]] is a 8 chain structure with sequence from [ | <table><tr><td colspan='2'>[[6vim]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Pseudomonas_putida Pseudomonas putida]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6VIM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6VIM FirstGlance]. <br> | ||
</td></tr><tr id=' | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2Å</td></tr> | ||
<tr id=' | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PBC:PHENYL+BORONIC+ACID'>PBC</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=6vim FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6vim OCA], [https://pdbe.org/6vim PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6vim RCSB], [https://www.ebi.ac.uk/pdbsum/6vim PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6vim ProSAT]</span></td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | |||
</table> | </table> | ||
== Function == | |||
[https://www.uniprot.org/uniprot/MANR_PSEPU MANR_PSEPU] | |||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
| Line 18: | Line 19: | ||
</div> | </div> | ||
<div class="pdbe-citations 6vim" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 6vim" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[Mandelate racemase|Mandelate racemase]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: | [[Category: Pseudomonas putida]] | ||
[[Category: Bearne | [[Category: Bearne SL]] | ||
[[Category: Grandinetti | [[Category: Grandinetti L]] | ||
[[Category: Sharma AN]] | |||
[[Category: Sharma | [[Category: St Maurice M]] | ||
[[Category: | |||
Revision as of 11:13, 11 October 2023
P. putida mandelate racemase co-crystallized with phenylboronic acidP. putida mandelate racemase co-crystallized with phenylboronic acid
Structural highlights
FunctionPublication Abstract from PubMedBoronic acids have been successfully employed as inhibitors of hydrolytic enzymes. Typically, an enzymatic nucleophile catalyzing hydrolysis adds to the electrophilic boron atom forming a tetrahedral species that mimics the intermediate(s)/transition state(s) for the hydrolysis reaction. We show that para-substituted phenylboronic acids (PBAs) are potent competitive inhibitors of mandelate racemase (MR), an enzyme that catalyzes a 1,1-proton transfer rather than a hydrolysis reaction. The Ki value for PBA was 1.8 +/- 0.1 muM, and p-Cl-PBA exhibited the most potent inhibition (Ki = 81 +/- 4 nM), exceeding the binding affinity of the substrate by approximately 4 orders of magnitude. Isothermal titration calorimetric studies with the wild-type, K166M, and H297N MR variants indicated that, of the two Bronsted acid-base catalysts Lys 166 and His 297, the former made the greater contribution to inhibitor binding. The X-ray crystal structure of the MR.PBA complex revealed the presence of multiple H-bonds between the boronic acid hydroxyl groups and the side chains of active site residues, as well as formation of a His 297 N(epsilon2)-B dative bond. The dramatic upfield change in chemical shift of 27.2 ppm in the solution-phase (11)B nuclear magnetic resonance spectrum accompanying binding of PBA by MR was consistent with an sp(3)-hybridized boron, which was also supported by density-functional theory calculations. These unprecedented findings suggest that, beyond substituting boron at carbon centers participating in hydrolysis reactions, substitution of boron at the acidic carbon center of a substrate furnishes a new approach for generating inhibitors of enzymes catalyzing the deprotonation of carbon acid substrates. Potent Inhibition of Mandelate Racemase by Boronic Acids: Boron as a Mimic of a Carbon Acid Center.,Sharma AN, Grandinetti L, Johnson ER, St Maurice M, Bearne SL Biochemistry. 2020 Aug 25;59(33):3026-3037. doi: 10.1021/acs.biochem.0c00478., Epub 2020 Aug 10. PMID:32786399[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
|
| ||||||||||||||||||