7jmr: Difference between revisions

<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7jmr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7jmr OCA], [https://pdbe.org/7jmr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7jmr RCSB], [https://www.ebi.ac.uk/pdbsum/7jmr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7jmr ProSAT]</span></td></tr>

Hydroxybenzoic acids, like gallic acid and protocatechuic acid, are highly abundant natural compounds. In biotechnology, they serve as critical precursors for various molecules in heterologous production pathways, but a major bottleneck is these acids' non-oxidative decarboxylation to hydroxybenzenes. Optimizing this step by pathway and enzyme engineering is tedious, partly because of the complicating cofactor dependencies of the commonly used prFMN-dependent decarboxylases. Here, we report the crystal structures (1.5-1.9 A) of two homologous fungal decarboxylases, AGDC1 from Arxula adenivorans, and PPP2 from Madurella mycetomatis. Remarkably, both decarboxylases are cofactor independent and are superior to prFMN-dependent decarboxylases when heterologously expressed in Saccharomyces cerevisiae. The organization of their active site, together with mutational studies, suggests a novel decarboxylation mechanism that combines acid-base catalysis and transition state stabilization. Both enzymes are trimers, with a central potassium binding site. In each monomer, potassium introduces a local twist in a beta-sheet close to the active site, which primes the critical H86-D40 dyad for catalysis. A conserved pair of tryptophans, W35 and W61, acts like a clamp that destabilizes the substrate by twisting its carboxyl group relative to the phenol moiety. These findings reveal AGDC1 and PPP2 as founding members of a so far overlooked group of cofactor independent decarboxylases and suggest strategies to engineer their unique chemistry for a wide variety of biotechnological applications.

Crystal structures of non-oxidative decarboxylases reveal a new mechanism of action with a catalytic dyad and structural twists.,Zeug M, Markovic N, Iancu CV, Tripp J, Oreb M, Choe JY Sci Rep. 2021 Feb 4;11(1):3056. doi: 10.1038/s41598-021-82660-z. PMID:33542397<ref>PMID:33542397</ref>

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

[[Category: Large Structures]]

[[Category: Choe J]]

[[Category: Iancu CV]]

[[Category: Markovic N]]

[[Category: Oreb M]]

[[Category: Tripp J]]

[[Category: Zeug M]]