6vim

<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>

== Function ==

[https://www.uniprot.org/uniprot/MANR_PSEPU MANR_PSEPU]

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== Publication Abstract from PubMed ==

Boronic 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<ref>PMID:32786399</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>

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== References ==

<references/>

[[Category: Pseudomonas putida]]