{PDOC51986}
{PS51986; GS_BETA_GRASP}
{PS51987; GS_CATALYTIC}
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* Glutamine synthetase (GS) beta-grasp and catalytic domains profiles *
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The glutamine  synthetases  (GSs;  EC  6.3.1.2,  also known as gamma-glutamyl:
ammonia ligases)  are  a  family  of  large  oligomeric enzymes catalyzing the
condensation of ammonium and glutamate, along with ATP, to form glutamine, the
principal source  of  nitrogen for protein and nucleic acid synthesis. Because
of their  critical role in nitrogen metabolism, these enzymes are found in all
forms of  life  from  primitive to higher organisms, and they may be among the
most ancient  functioning  enzymes  in  existence.  In  mammals,  the activity
eliminates cytotoxic ammonia, at the same time converting neurotoxic glutamate
to harmless  glutamine;  there  are  a  number  of links between changes in GS
activity and  neurodegenerative  disorders,  such  as  Alzheimer's disease. In
plants, because  of  its importance in the assimilation and re-assimilation of
ammonia, the  enzyme  is  a  target  of  some herbicides. GS is also a central
component of  bacterial  nitrogen  metabolism  and  a  potential  drug  target
[1,2,3,4,5,6,7,8].

The GS   family   can   be  divided  into  three  main  enzyme  types,  easily
distinguished by  length:  GSI with 360 amino acids on average, GSII with 450,
and GSIII  with  730.  All of them form multimeric proteins containing double-
ringed quaternary  structures composed of identical units: GSI- and GSIII-type
enzymes contain  12  identical  subunits,  whereas  GSII-  enzymes  contain 10
identical subunits  consisting  of  2  pentameric  rings. All three GS classes
contain a  homology region that consists of a regulatory N-terminal beta-grasp
domain and  a  catalytic  C-terminal domain, with the N-terminal domain of one
subunit and the C-terminal domain of the neighboring subunit forming an active
site. The  beta-grasp domain consists of a five-strand antiparallel beta-sheet
(see <PDB:3FKY>) whereas the catalytic domain contains an eight-stranded beta-
sheet (see <PDB:7CPR>) [1,2,3,4,5,6,7,8].

The profiles  we  developed  cover  the  entire  GS  beta-grasp  and catalytic
domains.

-Sequences known to belong to this class detected by the profile: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.

-Sequences known to belong to this class detected by the profile: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.

-Last update: February 2023 / Profile revised.

[ 1] Wyatt K., White H.E., Wang L., Bateman O.A., Slingsby C., Orlova E.V.,
     Wistow G.
     "Lengsin is a survivor of an ancient family of class I glutamine
     synthetases re-engineered by evolution for a role in the vertebrate
     lens."
     Structure 14:1823-1834(2006).
     PubMed=17161372; DOI=10.1016/j.str.2006.10.008
[ 2] Unno H., Uchida T., Sugawara H., Kurisu G., Sugiyama T., Yamaya T.,
     Sakakibara H., Hase T., Kusunoki M.
     "Atomic structure of plant glutamine synthetase: a key enzyme for
     plant productivity."
     J. Biol. Chem. 281:29287-29296(2006).
     PubMed=16829528; DOI=10.1074/jbc.M601497200
[ 3] He Y.-X., Gui L., Liu Y.-Z., Du Y., Zhou Y., Li P., Zhou C.-Z.
     "Crystal structure of Saccharomyces cerevisiae glutamine synthetase
     Gln1 suggests  a nanotube-like supramolecular assembly."
     Proteins 76:249-254(2009).
     PubMed=19322816; DOI=10.1002/prot.22403
[ 4] van Rooyen J.M., Abratt V.R., Belrhali H., Sewell T.
     "Crystal structure of Type III glutamine synthetase: surprising
     reversal of the inter-ring interface."
     Structure 19:471-483(2011).
     PubMed=21481771; DOI=10.1016/j.str.2011.02.001
[ 5] Qiu C., Hong Y., Cao Y., Wang F., Fu Z., Shi Y., Wei M., Liu S.,
     Lin J.
     "Molecular cloning and characterization of glutamine synthetase, a
     tegumental protein from Schistosoma japonicum."
     Parasitol. Res. 111:2367-2376(2012).
     PubMed=23011789; DOI=10.1007/s00436-012-3092-6
[ 6] Wagner D., Wiemann P., Huss K., Brandt U., Fleissner A., Tudzynski B.
     "A sensing role of the glutamine synthetase in the nitrogen regulation
     network in  Fusarium fujikuroi."
     PLoS One. 8:E80740-E80740(2013).
     PubMed=24260467; DOI=10.1371/journal.pone.0080740
[ 7] Lee B.N., Adams T.H.
     "The Aspergillus nidulans fluG gene is required for production of an
     extracellular developmental signal and is related to prokaryotic
     glutamine synthetase I."
     Genes. Dev. 8:641-651(1994).
     PubMed=7926755; DOI=10.1101/gad.8.6.641
[ 8] Kurihara S., Oda S., Tsuboi Y., Kim H.G., Oshida M., Kumagai H.,
     Suzuki H.
     "gamma-Glutamylputrescine synthetase in the putrescine utilization
     pathway of Escherichia coli K-12."
     J. Biol. Chem. 283:19981-19990(2008).
     PubMed=18495664; DOI=10.1074/jbc.M800133200

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