7ZU9

CRYSTAL STRUCTURE OF THE C89A_C113A GMP SYNTHETASE INACTIVE DOUBLE MUTANT FROM PLASMODIUM FALCIPARUM

Summary for 7ZU9

• Entry DOI: 10.2210/pdb7zu9/pdb
• Related: 4WIM 4WIN 4WIO
• Descriptor: Glutamine amidotransferase (2 entities in total)
• Functional Keywords: gmp synthetase, purine salvage pathway, ligase
• Biological source: Plasmodium falciparum 3D7
• Total number of polymer chains: 1
• Total formula weight: 65423.48

Authors

Ballut, L.,Violot, S.,Aghajari, N. (deposition date: 2022-05-11, release date: 2022-08-10, Last modification date: 2024-02-07)

Primary citation

Ballut, L.,Violot, S.,Galisson, F.,Goncalves, I.R.,Martin, J.,Shivakumaraswamy, S.,Carrique, L.,Balaram, H.,Aghajari, N.
Tertiary and Quaternary Structure Organization in GMP Synthetases: Implications for Catalysis.
Biomolecules, 12:-, 2022

PubMed Abstract: Glutamine amidotransferases, enzymes that transfer nitrogen from Gln to various cellular metabolites, are modular, with the amidotransferase (GATase) domain hydrolyzing Gln, generating ammonia and the acceptor domain catalyzing the addition of nitrogen onto its cognate substrate. GMP synthetase (GMPS), an enzyme in the de novo purine nucleotide biosynthetic pathway, is a glutamine amidotransferase that catalyzes the synthesis of GMP from XMP. The reaction involves activation of XMP though adenylation by ATP in the ATP pyrophosphatase (ATPPase) active site, followed by channeling and attack of NH generated in the GATase pocket. This complex chemistry entails co-ordination of activity across the active sites, allosteric activation of the GATase domain to modulate Gln hydrolysis and channeling of ammonia from the GATase to the acceptor active site. Functional GMPS dimers associate through the dimerization domain. The crystal structure of the Gln-bound complex of GMPS (GMPS) for the first time revealed large-scale domain rotation to be associated with catalysis and leading to the juxtaposition of two otherwise spatially distal cysteinyl (C113/C337) residues. In this manuscript, we report on an unusual structural variation in the crystal structure of the C89A/C113A GMPS double mutant, wherein a larger degree of domain rotation has led to the dissociation of the dimeric structure. Furthermore, we report a hitherto overlooked signature motif tightly related to catalysis.

PubMed: 35883427
DOI: 10.3390/biom12070871

Experimental method

X-RAY DIFFRACTION (2.8 Å)