Please note: this site relies heavily on the use of javascript. Without a javascript-enabled browser, this site will not function correctly. Please enable javascript and reload the page, or switch to a different browser.
37  structures 8504  species 0  interactions 10094  sequences 65  architectures

Family: GMP_synt_C (PF00958)

Summary: GMP synthase C terminal domain

Pfam includes annotations and additional family information from a range of different sources. These sources can be accessed via the tabs below.

This is the Wikipedia entry entitled "GMP synthase". More...

GMP synthase Edit Wikipedia article

GMP synthetase
(glutamine-hydrolyzing)
2vxo.jpg
GMP synthetase, human
Identifiers
EC no.6.3.5.2
CAS no.37318-71-1
Databases
IntEnzIntEnz view
BRENDABRENDA entry
ExPASyNiceZyme view
KEGGKEGG entry
MetaCycmetabolic pathway
PRIAMprofile
PDB structuresRCSB PDB PDBe PDBsum
Gene OntologyAmiGO / QuickGO
GMP synthetase C terminal domain
PDB 1gpm EBI.jpg
escherichia coli gmp synthetase complexed with amp and pyrophosphate.[1]
Identifiers
SymbolGMP_synt_C
PfamPF00958
InterProIPR001674
PROSITEPDOC00405
SCOP21gpm / SCOPe / SUPFAM
GMPS
Protein GMPS PDB 2VPI.png
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesGMPS, GMP synthase, guanine monophosphate synthase, GATD7, GMP synthase
External IDsOMIM: 600358 MGI: 2448526 HomoloGene: 68367 GeneCards: GMPS
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_003875

NM_001033300

RefSeq (protein)

NP_003866

NP_001028472

Location (UCSC)Chr 3: 155.87 – 155.94 MbChr 3: 63.98 – 64.02 Mb
PubMed search[4][5]
Wikidata
View/Edit HumanView/Edit Mouse

Guanosine monophosphate synthetase, (EC 6.3.5.2) also known as GMPS is an enzyme that converts xanthosine monophosphate to guanosine monophosphate.[6]

In the de novo synthesis of purine nucleotides, IMP is the branch point metabolite at which point the pathway diverges to the synthesis of either guanine or adenine nucleotides. In the guanine nucleotide pathway, there are 2 enzymes involved in converting IMP to GMP, namely IMP dehydrogenase (IMPD1), which catalyzes the oxidation of IMP to XMP, and GMP synthetase, which catalyzes the amination of XMP to GMP.[6]

Enzymology

In enzymology, a GMP synthetase (glutamine-hydrolysing) (EC 6.3.5.2) is an enzyme that catalyzes the chemical reaction

ATP + xanthosine 5'-phosphate + L-glutamine + H2O AMP + diphosphate + GMP + L-glutamate

The 4 substrates of this enzyme are ATP, xanthosine 5'-phosphate, L-glutamine, and H2O, whereas its 4 products are AMP, diphosphate, GMP, and L-glutamate.

This enzyme belongs to the family of ligases, specifically those forming carbon-nitrogen bonds carbon-nitrogen ligases with glutamine as amido-N-donor. The systematic name of this enzyme class is xanthosine-5'-phosphate:L-glutamine amido-ligase (AMP-forming). Other names in common use include GMP synthetase (glutamine-hydrolysing), guanylate synthetase (glutamine-hydrolyzing), guanosine monophosphate synthetase (glutamine-hydrolyzing), xanthosine 5'-phosphate amidotransferase, and guanosine 5'-monophosphate synthetase. This enzyme participates in purine metabolism and glutamate metabolism. At least one compound, Psicofuranin is known to inhibit this enzyme.

Structural studies

As of late 2007, 5 structures have been solved for this class of enzymes, with PDB accession codes 1GPM, 1WL8, 2A9V, 2D7J, and 2DPL.

Role in Metabolism

Purine Metabolism

GMP Synthase is the second step in the generation of GMP from IMP; the first step occurs when IMP dehydrogenase generates XMP, and then GMP synthetase is able to react with glutamine and ATP to generate GMP. IMP may also be generated into AMP by Adenylosuccinate synthetase and then adenylosuccinate lyase.[7]

Amino Acid Metabolism

GMP synthase is also involved in amino acid metabolism because it generates L-glutamate from L-glutamine.[7]

Organismal involvement

This enzyme is widely distributed and a number of crystal structures have been solved, including in Escherichia coli, Pyrococcus Horikoshii, Thermoplasma acidophil, Homo sapiens, Thermus thermophilus and Mycobacterium tuberculosis. The most extensive structural studies have been done in E. coli.[8]

Structure and Function

GMP synthase forms a tetramer in an open box shape, which is a dimer of dimers. The R interfaces are held together with a hydrophobic core and a beta sheet, while the P dimer interfaces do not have a hydrophobic core and are more variable than the R interfaces.[8] This enzyme also binds several ligands, including phosphate, pyrophosphate, AMP, citrate and Magnesium.[9]

Class I Amidotransferase Domain

The amidotransferase domain is responsible for removal of the amide nitrogen from the glutamine substrate. The class I amidotransferase domain is made of the N terminal 206 residues of the enzyme, and consists of 12 beta strands and 5 alpha helices; the core of this domain is an open 7-stranded mixed beta sheet. Its catalytic triad includes Cys86, His181 and Glu183. His181 is a base and Glu183 is a Hydrogen bond acceptor from the Histidine imidazole ring. Cys86 is the catalytic residue and is conserved. It falls into a nucleophile elbow, where it is at the end of a beta strand and the beginning of an alpha helix, and has little flexibility in its phi and psi angles; thus, Gly84 and Gly88 are conserved and allow for the tight packing of amino acids surrounding the catalytic residue.[8]

Synthetase Domain: ATP Pyrophosphatase domain

The synthetase domain is responsible for the addition of the abstracted Nitrogen to the acceptor substrate. The ATP Pyrophosphatase domain consists of a beta sheet containing 5 parallel strands with several alpha helices on each side. The P loop is the nucleotide binding motif; residues 235-241 make up the P loop which specifically binds to pyrophosphate.[8]

The structure of this domain is what creates the specificity of this enzyme for ATP. The binding pocket forms hydrophobic interactions with the adenine ring, and the backbone of Val260 forms H bonds with multiple Nitrogens in the ring of AMP, which excludes substituents on the C2 purine ring. This creates extreme specificity for adenine and ATP binding.[8]

References

  1. ^ Tesmer JJ, Klem TJ, Deras ML, Davisson VJ, Smith JL (January 1996). "The crystal structure of GMP synthetase reveals a novel catalytic triad and is a structural paradigm for two enzyme families". Nature Structural Biology. 3 (1): 74–86. doi:10.1038/nsb0196-74. PMID 8548458. S2CID 30864133.
  2. ^ a b c GRCh38: Ensembl release 89: ENSG00000163655 - Ensembl, May 2017
  3. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000027823 - Ensembl, May 2017
  4. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  6. ^ a b "Entrez Gene: GMPS guanine monphosphate synthetase".
  7. ^ a b Garrett RH (1998). Biochemistry. [Place of publication not identified]: Harcourt College. ISBN 0-03-044857-3. OCLC 947935503.
  8. ^ a b c d e Tesmer JJ, Klem TJ, Deras ML, Davisson VJ, Smith JL (January 1996). "The crystal structure of GMP synthetase reveals a novel catalytic triad and is a structural paradigm for two enzyme families". Nature Structural Biology. 3 (1): 74–86. doi:10.1038/nsb0196-74. PMID 8548458.
  9. ^ "Ligand/metal interactions: 1gpm". www.ebi.ac.uk. Retrieved 2021-10-21.

Further reading

  • Page T, Bakay B, Nyhan WL (1984). "Human GMP synthetase". The International Journal of Biochemistry. 16 (1): 117–20. doi:10.1016/0020-711X(84)90061-2. PMID 6698284.
  • Nakamura J, Straub K, Wu J, Lou L (October 1995). "The glutamine hydrolysis function of human GMP synthetase. Identification of an essential active site cysteine". The Journal of Biological Chemistry. 270 (40): 23450–5. doi:10.1074/jbc.270.40.23450. PMID 7559506.
  • Nakamura J, Lou L (March 1995). "Biochemical characterization of human GMP synthetase". The Journal of Biological Chemistry. 270 (13): 7347–53. doi:10.1074/jbc.270.13.7347. PMID 7706277.
  • Hirst M, Haliday E, Nakamura J, Lou L (September 1994). "Human GMP synthetase. Protein purification, cloning, and functional expression of cDNA". The Journal of Biological Chemistry. 269 (38): 23830–7. PMID 8089153.
  • Maruyama K, Sugano S (January 1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
  • Fedorova L, Kost-Alimova M, Gizatullin RZ, Alimov A, Zabarovska VI, Szeles A, et al. (1997). "Assignment and ordering of twenty-three unique NotI-linking clones containing expressed genes including the guanosine 5'-monophosphate synthetase gene to human chromosome 3". European Journal of Human Genetics. 5 (2): 110–6. doi:10.1159/000484744. PMID 9195163.
  • Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (October 1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1–2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
  • Pegram LD, Megonigal MD, Lange BJ, Nowell PC, Rowley JD, Rappaport EF, Felix CA (December 2000). "t(3;11) translocation in treatment-related acute myeloid leukemia fuses MLL with the GMPS (GUANOSINE 5' MONOPHOSPHATE SYNTHETASE) gene". Blood. 96 (13): 4360–2. doi:10.1182/blood.V96.13.4360. PMID 11110714.
  • Guo D, Han J, Adam BL, Colburn NH, Wang MH, Dong Z, et al. (December 2005). "Proteomic analysis of SUMO4 substrates in HEK293 cells under serum starvation-induced stress". Biochemical and Biophysical Research Communications. 337 (4): 1308–18. doi:10.1016/j.bbrc.2005.09.191. PMID 16236267.
  • Abrams R, Bentley M (1959). "Biosynthesis of nucleic acid purines. III. Guanosine 5'-phosphate formation from xanthosine 5'-phosphate and L-glutamine". Arch. Biochem. Biophys. 79: 91–110. doi:10.1016/0003-9861(59)90383-2.
  • Lagerkvist U (July 1958). "Biosynthesis of guanosine 5'-phosphate. II. Amination of xanthosine 5'-phosphate by purified enzyme from pigeon liver". The Journal of Biological Chemistry. 233 (1): 143–9. PMID 13563458.

External links

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.

GMP synthase C terminal domain Provide feedback

GMP synthetase is a glutamine amidotransferase from the de novo purine biosynthetic pathway. This family is the C-terminal domain specific to the GMP synthases P49915 EC:6.3.5.2. In prokaryotes this domain mediates dimerisation. Eukaryotic GMP synthases are monomers. This domain in eukaryotes includes several large insertions that may form globular domains.

Literature references

  1. Tesmer JJ, Klem TJ, Deras ML, Davisson VJ, Smith JL; , Nat Struct Biol 1996;3:74-86.: The crystal structure of GMP synthetase reveals a novel catalytic triad and is a structural paradigm for two enzyme families. PUBMED:8548458 EPMC:8548458


External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR001674

The amidotransferase family of enzymes utilises the ammonia derived from the hydrolysis of glutamine for a subsequent chemical reaction catalyzed by the same enzyme. The ammonia intermediate does not dissociate into solution during the chemical transformations [ PUBMED:10387030 ]. GMP synthetase is a glutamine amidotransferase from the de novo purine biosynthetic pathway. The C-terminal domain is specific to the GMP synthases EC . In prokaryotes this domain mediates dimerisation. Eukaryotic GMP synthases are monomers. This domain in eukaryotes includes several large insertions that may form globular domains [ PUBMED:8548458 ].

Gene Ontology

The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.

Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

Loading domain graphics...

Alignments

We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database (reference proteomes) using the family HMM. We also generate alignments using four representative proteomes (RP) sets and the UniProtKB sequence database. More...

View options

We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.

  Seed
(197)
Full
(10094)
Representative proteomes UniProt
(45762)
RP15
(1556)
RP35
(5019)
RP55
(10062)
RP75
(16675)
Jalview View  View  View  View  View  View  View 
HTML View             
PP/heatmap 1            

1Cannot generate PP/Heatmap alignments for seeds; no PP data available

Key: ✓ available, x not generated, not available.

Format an alignment

  Seed
(197)
Full
(10094)
Representative proteomes UniProt
(45762)
RP15
(1556)
RP35
(5019)
RP55
(10062)
RP75
(16675)
Alignment:
Format:
Order:
Sequence:
Gaps:
Download/view:

Download options

We make all of our alignments available in Stockholm format. You can download them here as raw, plain text files or as gzip-compressed files.

  Seed
(197)
Full
(10094)
Representative proteomes UniProt
(45762)
RP15
(1556)
RP35
(5019)
RP55
(10062)
RP75
(16675)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download  
Gzipped Download   Download   Download   Download   Download   Download   Download  

You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

HMM logo

HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...

Trees

This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.

Note: You can also download the data file for the tree.

Curation and family details

This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.

Curation View help on the curation process

Seed source: Pfam-B_1137 (release 3.0)
Previous IDs: none
Type: Domain
Sequence Ontology: SO:0000417
Author: Finn RD , Bateman A , Griffiths-Jones SR
Number in seed: 197
Number in full: 10094
Average length of the domain: 91.80 aa
Average identity of full alignment: 54 %
Average coverage of the sequence by the domain: 17.63 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 61295632 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 27.0 27.0
Trusted cut-off 27.1 27.0
Noise cut-off 26.9 26.9
Model length: 92
Family (HMM) version: 25
Download: download the raw HMM for this family

Species distribution

Sunburst controls

Hide

Weight segments by...


Change the size of the sunburst

Small
Large

Colour assignments

Archea Archea Eukaryota Eukaryota
Bacteria Bacteria Other sequences Other sequences
Viruses Viruses Unclassified Unclassified
Viroids Viroids Unclassified sequence Unclassified sequence

Selections

Align selected sequences to HMM

Generate a FASTA-format file

Clear selection

This visualisation provides a simple graphical representation of the distribution of this family across species. You can find the original interactive tree in the adjacent tab. More...

Loading sunburst data...

Tree controls

Hide

The tree shows the occurrence of this domain across different species. More...

Loading...

Please note: for large trees this can take some time. While the tree is loading, you can safely switch away from this tab but if you browse away from the family page entirely, the tree will not be loaded.

Structures

For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the GMP_synt_C domain has been found. There are 37 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein sequence.

Loading structure mapping...

AlphaFold Structure Predictions

The list of proteins below match this family and have AlphaFold predicted structures. Click on the protein accession to view the predicted structure.

Protein Predicted structure External Information
A0KJS0 View 3D Structure Click here
A0Q2S8 View 3D Structure Click here
A1AQJ8 View 3D Structure Click here
A1AXH0 View 3D Structure Click here
A1BD85 View 3D Structure Click here
A1K5U3 View 3D Structure Click here
A1S856 View 3D Structure Click here
A1SYT6 View 3D Structure Click here
A1URR0 View 3D Structure Click here
A2SG95 View 3D Structure Click here
A3DCD4 View 3D Structure Click here
A3MZV8 View 3D Structure Click here
A3PA84 View 3D Structure Click here
A3QCH0 View 3D Structure Click here
A4G4U7 View 3D Structure Click here
A4SGJ0 View 3D Structure Click here
A4XY17 View 3D Structure Click here
A4YSU1 View 3D Structure Click here
A5I720 View 3D Structure Click here
A5N5D9 View 3D Structure Click here
A5VLY3 View 3D Structure Click here
A6H0T6 View 3D Structure Click here
A6L686 View 3D Structure Click here
A6LD04 View 3D Structure Click here
A6Q4N8 View 3D Structure Click here
A6QBI5 View 3D Structure Click here
A6TCC2 View 3D Structure Click here
A6TLR3 View 3D Structure Click here
A6VMR9 View 3D Structure Click here
A7I131 View 3D Structure Click here
A7IA92 View 3D Structure Click here
A8AD80 View 3D Structure Click here
A8ETA7 View 3D Structure Click here
A8FAH5 View 3D Structure Click here
A8H254 View 3D Structure Click here
A8LAX2 View 3D Structure Click here
A8LKW5 View 3D Structure Click here
A9AIP4 View 3D Structure Click here
A9IKK0 View 3D Structure Click here
A9MHM5 View 3D Structure Click here