4R7G

Determination of the formylglycinamide ribonucleotide amidotransferase ammonia pathway by combining 3D-RISM theory with experiment

Summary for 4R7G

• Entry DOI: 10.2210/pdb4r7g/pdb
• Related: 1T3t
• Descriptor: Phosphoribosylformylglycinamidine synthase, MAGNESIUM ION, SULFATE ION, ... (5 entities in total)
• Functional Keywords: gene duplication, amidotransferase, atp binding, ligase
• Biological source: Salmonella typhimurium LT2
• Cellular location: Cytoplasm : P74881
• Total number of polymer chains: 1
• Total formula weight: 143656.93

Authors

Tanwar, A.S.,Sindhikara, D.J.,Hirata, F.,Anand, R. (deposition date: 2014-08-27, release date: 2015-01-21, Last modification date: 2023-11-08)

Primary citation

Tanwar, A.S.,Sindhikara, D.J.,Hirata, F.,Anand, R.
Determination of the formylglycinamide ribonucleotide amidotransferase ammonia pathway by combining 3D-RISM theory with experiment.
Acs Chem.Biol., 10:698-704, 2015

PubMed Abstract: 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 Å 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.

PubMed: 25551173
DOI: 10.1021/cb501015r

Experimental method

X-RAY DIFFRACTION (2.9 Å)