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We are deeply saddened by the passing of Amos Bairoch (1957–2025), the creator of PROSITE. We wish to dedicate our latest paper, published shortly before his death, to him. He will always be a source of inspiration to us.
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Amos Bairoch

PROSITE documentation PDOC51553
GMP synthetase ATP pyrophosphatase (GMPS ATP-PPase) domain profile


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PURL: https://purl.expasy.org/prosite/documentation/PDOC51553

Description

Guanosine 5'-monophosphate synthetase (GMPS) is a widespread enzyme seen in all domains of life. GMPS is required for the final step of the de novo synthesis of guanine nucleotides, converting xanthosine 5'-monophosphate (XMP) into guanosine 5'-monophosphate (GMP), a precursor of DNA and RNA. GMPS consists of two catalytic units, glutamine amidotransferase (GATase) (see <PDOC00405>) and ATP pyrophosphatase (ATP-PPase). GATase hydrolyzes glutamine to yield glutamate and ammonia, while ATP-PPase utilizes ammonia to convert adenyl xanthosine 5'-monophosphate (adenyl-XMP) into GMP. The two catalytic units are either encoded by a single gene (two-domain type) in eucaryotes, bacteria, and some archaea, or encoded by two separate genes (two-subunit type) in other archaea. In two-domain-type GMPS, the GATase domain is located in the N-terminal half, and the ATP-PPase domain is located in the C-terminal half; in two-subunit-type GMPS, these two units exist as separate polypeptides. ATP-PPase consists of two domains (N-domain and C-domain). The N-domain contains an ATP-binding platform called P-loop (see <PDOC00017>), whereas the C-domain contains the XMP-binding site and also contributes to homodimerization [1,2,3].

The GMP synthetase ATP-PPase ATP-binding domain is a twisted, five-stranded parallel β-sheet sandwiched between helical layers (see <PDB:1GPM>). It contains a glycine rich ATP-binding motif called the "P-loop motif" located after the first β-strand [1,3].

The profile we developed covers the entire GMPS ATP-PPase domain.

Last update:

November 2011 / First entry.

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Technical section

PROSITE method (with tools and information) covered by this documentation:

GMPS_ATP_PPASE, PS51553; GMP synthetase ATP pyrophosphatase (GMPS ATP-PPase) domain profile  (MATRIX)


References

1AuthorsTesmer J.J.G. Klem T.J. Deras M.L. Davisson V.J. Smith J.L.
TitleThe crystal structure of GMP synthetase reveals a novel catalytic triad and is a structural paradigm for two enzyme families.
SourceNat. Struct. Biol. 3:74-86(1996).
PubMed ID8548458

2AuthorsGrimaldi C. Dutertre M. Simonet J.-M.
TitleGenetic organization and polymorphism of the guaA gene encoding the GMP synthetase in Lactobacillus rhamnosus.
SourceCurr. Microbiol. 40:245-249(2000).
PubMed ID10688693
DOI10.1007/s002849910049

3AuthorsMaruoka S. Horita S. Lee W.C. Nagata K. Tanokura M.
TitleCrystal structure of the ATPPase subunit and its substrate-dependent association with the GATase subunit: a novel regulatory mechanism for a two-subunit-type GMP synthetase from Pyrococcus horikoshii OT3.
SourceJ. Mol. Biol. 395:417-429(2010).
PubMed ID19900465
DOI10.1016/j.jmb.2009.10.053



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