4I4C

Crystal structure of the protein frsA complexed with unknown ligand

Summary for 4I4C

• Entry DOI: 10.2210/pdb4i4c/pdb
• Related: 3MVE 3OUR
• Descriptor: UPF0255 protein frsA, 2-(2-{2-[2-(2-METHOXY-ETHOXY)-ETHOXY]-ETHOXY}-ETHOXY)-ETHANOL, HEXANOIC ACID, ... (5 entities in total)
• Functional Keywords: two-domain protein frsa, unknown function, unknown ligand
• Biological source: Vibrio vulnificus
• Total number of polymer chains: 2
• Total formula weight: 94976.73

Authors

Fedorov, A.A.,Fedorov, E.V.,Desai, B.,Gerlt, J.A.,Richards, N.,Almo, S.C. (deposition date: 2012-11-27, release date: 2013-10-09, Last modification date: 2023-09-20)

Primary citation

Kellett, W.F.,Brunk, E.,Desai, B.J.,Fedorov, A.A.,Almo, S.C.,Gerlt, J.A.,Rothlisberger, U.,Richards, N.G.
Computational, structural, and kinetic evidence that Vibrio vulnificus FrsA is not a cofactor-independent pyruvate decarboxylase.
Biochemistry, 52:1842-1844, 2013

PubMed Abstract: The fermentation-respiration switch (FrsA) protein in Vibrio vulnificus was recently reported to catalyze the cofactor-independent decarboxylation of pyruvate. We now report quantum mechanical/molecular mechenical calculations that examine the energetics of C-C bond cleavage for a pyruvate molecule bound within the putative active site of FrsA. These calculations suggest that the barrier to C-C bond cleavage in the bound substrate is 28 kcal/mol, which is similar to that estimated for the uncatalyzed decarboxylation of pyruvate in water at 25 °C. In agreement with the theoretical predictions, no pyruvate decarboxylase activity was detected for recombinant FrsA protein that could be crystallized and structurally characterized. These results suggest that the functional annotation of FrsA as a cofactor-independent pyruvate decarboxylase is incorrect.

PubMed: 23452154
DOI: 10.1021/bi400093y

Experimental method

X-RAY DIFFRACTION (1.95 Å)