Structural highlights
Function
PUR4_SALTY
Publication Abstract from PubMed
Molecular tunnels in enzyme systems possess variable architecture and are therefore difficult to predict. In this work, we design and apply an algorithm to resolve the pathway followed by ammonia using the bifunctional enzyme formylglycinamide ribonucleotide amidotransferase (FGAR-AT) as a model system. Though its crystal structure has been determined, an ammonia pathway connecting the glutaminase domain to the 30 A distal FGAR/ATP binding site remains elusive. Crystallography suggested two purported paths: an N-terminal-adjacent path (path 1) and an auxiliary ADP-adjacent path (path 2). The algorithm presented here, RismPath, which enables fast and accurate determination of solvent distribution inside a protein channel, predicted path 2 as the preferred mode of ammonia transfer. Supporting experimental studies validate the identity of the path, and results lead to the conclusion that the residues in the middle of the channel do not partake in catalytic coupling and serve only as channel walls facilitating ammonia transfer.
Determination of the Formylglycinamide Ribonucleotide Amidotransferase Ammonia Pathway by Combining 3D-RISM Theory with Experiment.,Tanwar AS, Sindhikara DJ, Hirata F, Anand R ACS Chem Biol. 2015 Jan 14. PMID:25551173[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Tanwar AS, Sindhikara DJ, Hirata F, Anand R. Determination of the Formylglycinamide Ribonucleotide Amidotransferase Ammonia Pathway by Combining 3D-RISM Theory with Experiment. ACS Chem Biol. 2015 Jan 14. PMID:25551173 doi:http://dx.doi.org/10.1021/cb501015r