Abstract:
"This chapter describes key features of glutamine amidotransferases
(GATs). Glutamine amidotransferases are the enzymes that transfer ammonia
derived from glutamine to various acceptor substrates. Apart from having a
central role in metabolism and their potential as drug targets, these enzymes have
been an area of active investigation for many decades for their fascinating
biochemistry. Large conformational dynamics, coordinated domain-cross talk and
ammonia channeling are some of the defining features of this family of enzymes.
Amidotransferases are represented by a large group of enzymes and have been
classified into three classes. A brief account of their classification along with their
role in various biosynthetic pathways is presented in this chapter. GMP synthetase
(GMPS), one of the members of this family of enzymes is the subject of the
present study. GMP synthetase catalyzes the conversion of XMP to GMP. The
enzyme contains two distinct catalytic sites, GATase (site for ammonia production
from glutamine) and ATPPase (the site for XMP amination). The two sites are
present in two domains within a single polypeptide chain as in all prokaryotic,
eukaryotic and a few members of archaeal GMPS. In most archaeal GMP
synthetases, the two sites are present in two separate polypeptides that are coded
for by two different genes. The two domain type GMP synthetases have been
studied in some detail while the two subunit type GMPS has remained largely
unexplored except for a single study on P. horikoshii GMPS. Current study
investigates the mechanism of subunit association, catalysis and ammonia
channeling in a two-subunit-type GMP synthetase from Methanocaldococcus
jannaschii, a hyperthermophilc archaeon. Studies on the structural and functional
aspects of GMPS synthetases from other organisms have also been discussed."
