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Formylglycinamide ribonucleotide amidotransferase from Salmonella typhimurium: role of ATP complexation and the glutaminase domain in catalytic coupling

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Title Formylglycinamide ribonucleotide amidotransferase from Salmonella typhimurium: role of ATP complexation and the glutaminase domain in catalytic coupling
 
Creator TANWAR, AS
MORAR, M
PANJIKAR, S
ANAND, R
 
Subject PURINE BIOSYNTHETIC-PATHWAY
GLYCEROL PHOSPHATE SYNTHASE
THERMOTOGA-MARITIMA
BACILLUS-SUBTILIS
CRYSTAL-STRUCTURE
SYNTHETASE
SUBSTRATE
AMMONIA
CRYSTALLOGRAPHY
PRODUCT
 
Description Formylglycinamide ribonucleotide (FGAR) amidotransferase (FGAR-AT) takes part in purine biosynthesis and is a multidomain enzyme with multiple spatially separated active sites. FGAR-AT contains a glutaminase domain that is responsible for the generation of ammonia from glutamine. Ammonia is then transferred via a channel to a second active site located in the synthetase domain and utilized to convert FGAR to formylglycinamidine ribonucleotide (FGAM) in an adenosine triphosphate (ATP) dependent reaction. In some ammonia-channelling enzymes ligand binding triggers interdomain signalling between the two diverse active centres and also assists in formation of the ammonia channel. Previously, the structure of FGAR-AT from Salmonella typhimurium containing a glutamyl thioester intermediate covalently bound in the glutaminase active site was determined. In this work, the roles played by various ligands of FGAR-AT in inducing catalytic coupling are investigated. Structures of FGAR-AT from S. typhimurium were determined in two different states: the unliganded form and the binary complex with an ATP analogue in the presence of the glutamyl thioester intermediate. The structures were compared in order to decipher the roles of these two states in interdomain communication. Using a process of elimination, the results indicated that binding of FGAR is most likely to be the major mechanism by which catalytic coupling occurs. This is because conformational changes do not occur either upon formation of the glutamyl thioester intermediate or upon subsequent ATP complexation. A model of the FGAR-bound form of the enzyme suggested that the loop in the synthetase domain may be responsible for initiating catalytic coupling via its interaction with the N-terminal domain.
 
Publisher WILEY-BLACKWELL
 
Date 2014-10-14T17:10:21Z
2014-10-14T17:10:21Z
2012
 
Type Article
 
Identifier ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY, 68627-636
http://dx.doi.org/10.1107/S0907444912006543
http://dspace.library.iitb.ac.in/jspui/handle/100/14533
 
Language en