gltA

168

large subunit of [metabolite|glutamate] synthase, controls [protein|C36C8C9EEDCAD392D9BEC9728A1E0CBFF2F4E790|gudB] activity

locus: BSU_18450

Molecular weight: 168.61 kDa

pI: 5.47

Protein length: 1520 aa

Gene length: 4563 bp

function: [metabolite|glutamate] biosynthesis and control of [metabolite|glutamate] degradation

product: [metabolite|glutamate] synthase (large subunit)

essential: no

ec: 1.4.1.13

synonyms: gltA

List of homologs in different organisms, belongs to COG0070 (Galperin et al., 2021)

Gene

Coordinates: 2,010,070  2,014,632

Phenotypes of a mutant

• auxotrophic for [metabolite|glutamate] [pubmed|38483038], can be bypassed by inactivation of [gene|A3A2EF3C95B833A11843553107D781EDEFF0BC41|citG] and [gene|146947C974D62BCB282BA3F5B924B35695D75886|ansR] (as a result of [gene|FED8E46AA1C4EFD27796D5DFBBB1663EBF336BFD|ansA]-[gene|5FAE80F22AEBAE63FC3C872EC651166A65C34DC2|ansB] derepression)[pubmed|38483038]

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The protein

Catalyzed reaction/ biological activity

• 2 L-[metabolite|glutamate] + [metabolite|NADP]⁺ --> [metabolite|2-oxoglutarate] + H⁺ + L-[metabolite|glutamine] + [metabolite|NADPH] (according to UniProt)
• binding to [protein|C36C8C9EEDCAD392D9BEC9728A1E0CBFF2F4E790|gudB] to inhibit [metabolite|glutamate] degradation in the absence of [metabolite|glutamate] [pubmed|34931064]

Protein family

• glutamate synthase family (with [protein|D1AF9DA2594D2E2A94DC207A870C8495954A7A17|yerD] and [protein|AA07CC52B2DD48ACC9D3375E9D531CB1ACBE485A|gltB], according to UniProt)

[wiki|Domains]

• [wiki|Glutamine amidotransferase type-2 domain] (aa 22-415) (according to UniProt)
• Nucleotide binding domain (1060-1112)

[wiki|Cofactors]

• one [metabolite|3Fe-4S] cluster [pubmed|29292548]
• [metabolite|FMN] [pubmed|34931064]

Structure

• [PDB|7MFT] (the [protein|C36C8C9EEDCAD392D9BEC9728A1E0CBFF2F4E790|gudB]₆-([protein|44DF1B7E476AD58B3CCC39300FFE0132D0D32AD0|gltA]-[protein|AA07CC52B2DD48ACC9D3375E9D531CB1ACBE485A|gltB])₆ complex) [pubmed|34931064]
• [PDB|2VDC] (the [protein|44DF1B7E476AD58B3CCC39300FFE0132D0D32AD0|gltA]-[protein|AA07CC52B2DD48ACC9D3375E9D531CB1ACBE485A|gltB] complex of ''Azospirillum brasiliense'') [Pubmed|18199747], note that the B. subtilis protein is unable to form dimers, thus [protein|44DF1B7E476AD58B3CCC39300FFE0132D0D32AD0|gltA]-[protein|AA07CC52B2DD48ACC9D3375E9D531CB1ACBE485A|gltB] exists as a heterodimer [pubmed|34931064]
• [AF|P39812]

Modification

• phosphorylated on Arg-904 AND/OR Arg-914 [Pubmed|22517742]

Paralogous protein(s)

• [protein|D1AF9DA2594D2E2A94DC207A870C8495954A7A17|yerD]

[wiki|Localization]

• membrane associated [pubmed|18763711], cytoplasm (according to UniProt)

Additional information

• subject to Clp-dependent proteolysis upon [metabolite|glucose] starvation [PubMed|17981983]
• [wiki|translation] is likely to require [protein|3054CD45713BBD69C2A528DE24AF6AF37175FD9D|efp] due to the presence of several consecutive [metabolite|proline] residues [Pubmed|23239624,23239623]

Expression and Regulation

Operons

• genes: [gene|44DF1B7E476AD58B3CCC39300FFE0132D0D32AD0|gltA]-[gene|AA07CC52B2DD48ACC9D3375E9D531CB1ACBE485A|gltB]

  description: [Pubmed|12823818]

  regulation

  • expressed in the presence of ammonium [Pubmed|11029411]

  regulatory mechanism

  • [protein|857EF1AC54DEA0690C01B7F8CEFFD16312C58F20|tnrA]: repression, [Pubmed|11029411], in [regulon|protein:857EF1AC54DEA0690C01B7F8CEFFD16312C58F20|tnrA regulon]
  • [protein|87BCAE725B02860156D50E1783F6DB68510C811E|gltC]: activation, [Pubmed|2548995], in [regulon|protein:87BCAE725B02860156D50E1783F6DB68510C811E|gltC regulon]
  • [protein|F899F1EE27E6D503BCC06BC52E3C7FD80B8EF725|fur]: indirect effect, in [regulon|protein:F899F1EE27E6D503BCC06BC52E3C7FD80B8EF725|fur regulon]

  sigma factors

  • [protein|360F48D576DE950DF79C1A2677B7A35A8D8CC30C|sigA]: sigma factor, [Pubmed|2548995], in [regulon|protein:360F48D576DE950DF79C1A2677B7A35A8D8CC30C|sigA regulon]

Other regulations

• [protein|CE542AE1A32CCD1ABB259E6159F7A37A8078E189|fsrA]: translation inhibition, [Pubmed|22389480]

Biological materials

Mutant

• GP3906 (Δ[gene|44DF1B7E476AD58B3CCC39300FFE0132D0D32AD0|gltA]::aphA3), available in [wiki|Jörg Stülke]'s lab
• BP123 (Δ[gene|44DF1B7E476AD58B3CCC39300FFE0132D0D32AD0|gltA]-[gene|AA07CC52B2DD48ACC9D3375E9D531CB1ACBE485A|gltB]::''ermC'') , available in [wiki|Fabian Commichau]'s lab
• GP807 (Δ[gene|44DF1B7E476AD58B3CCC39300FFE0132D0D32AD0|gltA]-[gene|AA07CC52B2DD48ACC9D3375E9D531CB1ACBE485A|gltB]::''tet'') , available in [wiki|Jörg Stülke]'s lab
• GP222 (''gltA'' under the control of p-xyl), available in [wiki|Jörg Stülke]'s lab
• 1A808 ( ''gltA''::''cat''), [Pubmed|15109830], available at [http://pasture.asc.ohio-state.edu/BGSC/getdetail.cfm?bgscid=1A808&Search=1A808 BGSC]
• 1A809 ( ''gltA''::''kan''), [Pubmed|15109830], available at [http://pasture.asc.ohio-state.edu/BGSC/getdetail.cfm?bgscid=1A809&Search=1A809 BGSC]
• BKE18450 ([gene|44DF1B7E476AD58B3CCC39300FFE0132D0D32AD0|gltA]::erm  trpC2) available at [http://bgsc.org/getdetail.php?bgscid=BKE18450 BGSC],  [Pubmed|28189581], upstream reverse: _UP1_CATAATTCCTCTCCCCCGAT,  downstream forward: _UP4_GTACAGTAAGGAAGGGGAGA
• BKK18450 ([gene|44DF1B7E476AD58B3CCC39300FFE0132D0D32AD0|gltA]::kan  trpC2) available at [http://bgsc.org/getdetail.php?bgscid=BKK18450 BGSC],  [Pubmed|28189581], upstream reverse: _UP1_CATAATTCCTCTCCCCCGAT,  downstream forward: _UP4_GTACAGTAAGGAAGGGGAGA

two-hybrid system

• ''B. pertussis'' adenylate cyclase-based bacterial two hybrid system ([wiki|BACTH]), available in [wiki|Jörg Stülke]'s lab

lacZ fusion

• pGP526 (in [wiki|pAC7]), available in [wiki|Jörg Stülke]'s lab [pubmed|14523131]
• pGP919 (in [wiki|pAC5]), available in [wiki|Jörg Stülke]'s lab [pubmed|17183217]

labs

• [wiki|Linc Sonenshein], Tufts University, Boston, MA, USA [http://www.tufts.edu/sackler/microbiology/faculty/sonenshein/index.html Homepage]
• [wiki|Jörg Stülke], University of Göttingen, Germany [http://wwwuser.gwdg.de/~genmibio/stuelke.html Homepage]
• [wiki|Fabian Commichau] Brandenburg Technical University Cottbus-Senftenberg, Germany [http://genmibio.uni-goettingen.de/index.php?id=130 Homepage]

References

Reviews

• 16143852,12859215,22625175,12859215,34931063,35132259

Original Publications

• 12823818,18199747,11029411,12850135,7559360,15150225,2548995,17183217,17608797,17134717,14523131,12823818,18326565,17981983,18763711,20933603,17012385,22389480,22517742,25755103,28294562,28386026,29242163,11967268,31649652,32393519,34931064,38483038