PF3D7_1012600 (GMPS)

Genome location: Pf3D7_10_v3:481,939..484,906(-)

Genome classification: Core

Function and Localization

Product Description: GMP synthase [glutamine-hydrolyzing]

SignalP Peptide: N/A

# Transmembrane Domains: 0

EC Numbers: 6.3.5.2 (GMP synthase (glutamine-hydrolyzing))

Curated GO (PlasmoDB):

Type	GO Term	Name
Component	GO:0005829	cytosol
Function	GO:0003922	GMP synthase (glutamine-hydrolyzing) activity
Function	GO:0003921	GMP synthase activity
Process	GO:0006177	GMP biosynthetic process
Process	GO:0006164	purine nucleotide biosynthetic process

Expression by stage (LR - Le Roch et al., and MCA - Malaria Cell Atlas):

Stage	LR class	MCA mean	MCA prop. zeros
Sporozoite	not expressed	N/A	N/A
Ring	expressed	0.36	0.82
Trophozoite	expressed	0.27	0.84
Schizont	expressed	0.06	0.96
Gametocyte	expressed	0.12	0.93

More info:

Resistome Mutations

Old (Pf3D7v3) Gene ID: PF3D7_1012600

Resistome Missense Mutations: None

Resistome Compounds with Missense Mutations: None

Resistome # Samples with Disruptive Mutations: 0 (0 missense, 0 "interesting" missense)

Essentiality (ABS)

Zhang Phenotype: Non - Mutable in CDS

MIS: 0.125 | MFS: -2.925 | #Insertions: 0

PlasmoGEM Phenotype: Slow (Pb ortholog: PBANKA_1211000)

Relative Growth Rate: 0.64 ± 0.14
Confidence: 5.38

RMgmDB ABS Phenotype: Different from wild type (Pb ortholog: PBANKA_1211000)

Modification: Disrupted | RMgm-3223

More info: PhenoPlasm Link

Binding Evidence

AlphaFill Uniprot ID: Q8IJR9

"Best" AlphaFill ligand hit: XMP (xanthosine-5'-monophosphate, Local RMSD=0.83) with 3UOW (Global RMSD=1.62)

BRENDA EC Inhibitors:

EC #	Name	EC Inhibitors
6.3.5.2	GMP synthase (glutamine-hydrolysing)	ATPADPAMPGTPGDPCTPCMPGMPIMPXMPcAMPcGMP...

Orthology to BindingDB Entries:

UniProt	Protein Name	Species	Homology Source	BindingDB Ligands
Q3THK7	GMP synthase [glutamine-hydrolyzing]	Mus musculus	OMA, OrthoDB	CHEMBL127366
Q93008	Probable ubiquitin carboxyl-terminal hydrolase FAF-X	Homo sapiens	OrthoDB	CHEMBL1923233CHEMBL3114085CHEMBL1923233

Orthology Information

Ortholog Group (OrthoMCL): OG6_100862

Most Similar Human Ortholog: P49915

TM-align score: 0.76 | RMSD: 4.17

Seq Identity: 0.29 | Length: 510 / 555

All Human Orthologs (OrthoMCL):

Gene ID	Description
ENSG00000163655	guanine monophosphate synthase

Protein Information

Protein Length: 555 | Molecular Weight (kDa): 63.932

UniProt ID(s): Q8IJR9, Q9U775

PDB ID(s): 3UOW, 4WIM, 4WIN, 4WIO, 7ZU9

Isoelectric Point: 6.38

Protein Domain Annotations:

Source	Family ID	Description
InterPro	IPR001674	GMP synthase, C-terminal
InterPro	IPR004739	GMP synthase, glutamine amidotransferase
InterPro	IPR017926	Glutamine amidotransferase
InterPro	IPR022310	NAD/GMP synthase
InterPro	IPR022955	GMP synthase
InterPro	IPR029062	Class I glutamine amidotransferase-like
PFam	PF00117	Glutamine amidotransferase
PFam	PF00958	GMP synthase, C-terminal
PFam	PF02540	NAD/GMP synthase
Superfamily	SSF52317	Class I glutamine amidotransferase-like
Superfamily	SSF52402
Superfamily	SSF54810

Genetic Variation

MalariaGEN Pf7 (worldwide samples) # unique SNV/indels:

Homozygous genotype calls only

variant type	common	rare	doubleton	singleton
synonymous	5	33	9	37
disruptive	8	33	37	53
missense	8	32	37	48

Any inclusion in genotype call

variant type	common	rare	doubleton	singleton
synonymous	12	55	19	50
disruptive	11	97	46	98
missense	11	86	40	78

PlasmoDB Total SNPs: 151

Non-coding: 118 | Synonymous: 26 | Nonsynonymous: 7 | Stop Codon: 0

PMID	Title	Authors	DOI/Link
12368864	Genome sequence of the human malaria parasite Plasmodium falciparum.	Gardner MJ, Hall N, ..., Barrell B	10.1038/nature01097
17868038	Kinetic and biochemical characterization of Plasmodium falciparum GMP synthetase.	Bhat JY, Shastri BG, Balaram H	10.1042/BJ20070996
26592566	Active site coupling in Plasmodium falciparum GMP synthetase is triggered bydomain rotation.	Ballut L, Violot S, ..., Aghajari N	10.1038/ncomms9930