Glutamine synthetase

Details

Name
Glutamine synthetase
Synonyms
  • 6.3.1.2
  • glnA
  • Glutamate--ammonia ligase
  • Glutamine synthetase I beta
  • GS
  • GSI beta
Gene Name
glnA1
Organism
Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
Amino acid sequence
>lcl|BSEQ0051140|Glutamine synthetase
MTEKTPDDVFKLAKDEKVEYVDVRFCDLPGIMQHFTIPASAFDKSVFDDGLAFDGSSIRG
FQSIHESDMLLLPDPETARIDPFRAAKTLNINFFVHDPFTLEPYSRDPRNIARKAENYLI
STGIADTAYFGAEAEFYIFDSVSFDSRANGSFYEVDAISGWWNTGAATEADGSPNRGYKV
RHKGGYFPVAPNDQYVDLRDKMLTNLINSGFILEKGHHEVGSGGQAEINYQFNSLLHAAD
DMQLYKYIIKNTAWQNGKTVTFMPKPLFGDNGSGMHCHQSLWKDGAPLMYDETGYAGLSD
TARHYIGGLLHHAPSLLAFTNPTVNSYKRLVPGYEAPINLVYSQRNRSACVRIPITGSNP
KAKRLEFRSPDSSGNPYLAFSAMLMAGLDGIKNKIEPQAPVDKDLYELPPEEAASIPQTP
TQLSDVIDRLEADHEYLTEGGVFTNDLIETWISFKRENEIEPVNIRPHPYEFALYYDV
Number of residues
478
Molecular Weight
53569.475
Theoretical pI
Not Available
GO Classification
Functions
ATP binding / fibronectin binding / glutamate-ammonia ligase activity / metal ion binding / zymogen binding
Processes
evasion or tolerance of host immune response / glutamine biosynthetic process / growth / interaction with host via substance in symbiont surface / nitrogen fixation / pathogenesis / positive regulation of plasminogen activation
Components
cell wall / cytosol / extracellular region / plasma membrane
General Function
Involved in nitrogen metabolism via ammonium assimilation. Catalyzes the ATP-dependent biosynthesis of glutamine from glutamate and ammonia (PubMed:7937767, PubMed:12819079). Also able to use GTP (PubMed:7937767). D-glutamate is a poor substrate, and DL-glutamate shows about 50% of the standard specific activity (PubMed:7937767). Also plays a key role in controlling the ammonia levels within infected host cells and so contributes to the pathogens capacity to inhibit phagosome acidification and phagosome-lysosome fusion (PubMed:7937767, PubMed:12819079). Involved in cell wall biosynthesis via the production of the major component poly-L-glutamine (PLG) (PubMed:7937767, PubMed:10618433). PLG synthesis in the cell wall occurs only in nitrogen limiting conditions and on the contrary high nitrogen conditions inhibit PLG synthesis (Probable).
Specific Function
Atp binding
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Cytoplasm
Gene sequence
>lcl|BSEQ0051141|Glutamine synthetase (glnA1)
GTGACGGAAAAGACGCCCGACGACGTCTTCAAACTTGCCAAGGACGAGAAGGTCGAATAT
GTCGACGTCCGGTTCTGTGACCTGCCTGGCATCATGCAGCACTTCACGATTCCGGCTTCG
GCCTTTGACAAGAGCGTGTTTGACGACGGCTTGGCCTTTGACGGCTCGTCGATTCGCGGG
TTCCAGTCGATCCACGAATCCGACATGTTGCTTCTTCCCGATCCCGAGACGGCGCGCATC
GACCCGTTCCGCGCGGCCAAGACGCTGAATATCAACTTCTTTGTGCACGACCCGTTCACC
CTGGAGCCGTACTCCCGCGACCCGCGCAACATCGCCCGCAAGGCCGAGAACTACCTGATC
AGCACTGGCATCGCCGACACCGCATACTTCGGCGCCGAGGCCGAGTTCTACATTTTCGAT
TCGGTGAGCTTCGACTCGCGCGCCAACGGCTCCTTCTACGAGGTGGACGCCATCTCGGGG
TGGTGGAACACCGGCGCGGCGACCGAGGCCGACGGCAGTCCCAACCGGGGCTACAAGGTC
CGCCACAAGGGCGGGTATTTCCCAGTGGCCCCCAACGACCAATACGTCGACCTGCGCGAC
AAGATGCTGACCAACCTGATCAACTCCGGCTTCATCCTGGAGAAGGGCCACCACGAGGTG
GGCAGCGGCGGACAGGCCGAGATCAACTACCAGTTCAATTCGCTGCTGCACGCCGCCGAC
GACATGCAGTTGTACAAGTACATCATCAAGAACACCGCCTGGCAGAACGGCAAAACGGTC
ACGTTCATGCCCAAGCCGCTGTTCGGCGACAACGGGTCCGGCATGCACTGTCATCAGTCG
CTGTGGAAGGACGGGGCCCCGCTGATGTACGACGAGACGGGTTATGCCGGTCTGTCGGAC
ACGGCCCGTCATTACATCGGCGGCCTGTTACACCACGCGCCGTCGCTGCTGGCCTTCACC
AACCCGACGGTGAACTCCTACAAGCGGCTGGTTCCCGGTTACGAGGCCCCGATCAACCTG
GTCTATAGCCAGCGCAACCGGTCGGCATGCGTGCGCATCCCGATCACCGGCAGCAACCCG
AAGGCCAAGCGGCTGGAGTTCCGAAGCCCCGACTCGTCGGGCAACCCGTATCTGGCGTTC
TCGGCCATGCTGATGGCAGGCCTGGACGGTATCAAGAACAAGATCGAGCCGCAGGCGCCC
GTCGACAAGGATCTCTACGAGCTGCCGCCGGAAGAGGCCGCGAGTATCCCGCAGACTCCG
ACCCAGCTGTCAGATGTGATCGACCGTCTCGAGGCCGACCACGAATACCTCACCGAAGGA
GGGGTGTTCACAAACGACCTGATCGAGACGTGGATCAGTTTCAAGCGCGAAAACGAGATC
GAGCCGGTCAACATCCGGCCGCATCCCTACGAATTCGCGCTGTACTACGACGTTTAA
Chromosome Location
Not Available
Locus
Not Available
External Identifiers
ResourceLink
UniProtKB IDP9WN39
UniProtKB Entry NameGLN1B_MYCTU
General References
  1. Harth G, Horwitz MA: Expression and efficient export of enzymatically active Mycobacterium tuberculosis glutamine synthetase in Mycobacterium smegmatis and evidence that the information for export is contained within the protein. J Biol Chem. 1997 Sep 5;272(36):22728-35. [Article]
  2. Cole ST, Brosch R, Parkhill J, Garnier T, Churcher C, Harris D, Gordon SV, Eiglmeier K, Gas S, Barry CE 3rd, Tekaia F, Badcock K, Basham D, Brown D, Chillingworth T, Connor R, Davies R, Devlin K, Feltwell T, Gentles S, Hamlin N, Holroyd S, Hornsby T, Jagels K, Krogh A, McLean J, Moule S, Murphy L, Oliver K, Osborne J, Quail MA, Rajandream MA, Rogers J, Rutter S, Seeger K, Skelton J, Squares R, Squares S, Sulston JE, Taylor K, Whitehead S, Barrell BG: Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence. Nature. 1998 Jun 11;393(6685):537-44. [Article]
  3. Harth G, Clemens DL, Horwitz MA: Glutamine synthetase of Mycobacterium tuberculosis: extracellular release and characterization of its enzymatic activity. Proc Natl Acad Sci U S A. 1994 Sep 27;91(20):9342-6. [Article]
  4. Harth G, Zamecnik PC, Tang JY, Tabatadze D, Horwitz MA: Treatment of Mycobacterium tuberculosis with antisense oligonucleotides to glutamine synthetase mRNA inhibits glutamine synthetase activity, formation of the poly-L-glutamate/glutamine cell wall structure, and bacterial replication. Proc Natl Acad Sci U S A. 2000 Jan 4;97(1):418-23. [Article]
  5. Harth G, Horwitz MA: Inhibition of Mycobacterium tuberculosis glutamine synthetase as a novel antibiotic strategy against tuberculosis: demonstration of efficacy in vivo. Infect Immun. 2003 Jan;71(1):456-64. [Article]
  6. Tullius MV, Harth G, Horwitz MA: Glutamine synthetase GlnA1 is essential for growth of Mycobacterium tuberculosis in human THP-1 macrophages and guinea pigs. Infect Immun. 2003 Jul;71(7):3927-36. [Article]
  7. Mehta R, Pearson JT, Mahajan S, Nath A, Hickey MJ, Sherman DR, Atkins WM: Adenylylation and catalytic properties of Mycobacterium tuberculosis glutamine synthetase expressed in Escherichia coli versus mycobacteria. J Biol Chem. 2004 May 21;279(21):22477-82. Epub 2004 Mar 22. [Article]
  8. Kelkar DS, Kumar D, Kumar P, Balakrishnan L, Muthusamy B, Yadav AK, Shrivastava P, Marimuthu A, Anand S, Sundaram H, Kingsbury R, Harsha HC, Nair B, Prasad TS, Chauhan DS, Katoch K, Katoch VM, Kumar P, Chaerkady R, Ramachandran S, Dash D, Pandey A: Proteogenomic analysis of Mycobacterium tuberculosis by high resolution mass spectrometry. Mol Cell Proteomics. 2011 Dec;10(12):M111.011627. doi: 10.1074/mcp.M111.011445. Epub 2011 Oct 3. [Article]
  9. Gill HS, Pfluegl GM, Eisenberg D: Multicopy crystallographic refinement of a relaxed glutamine synthetase from Mycobacterium tuberculosis highlights flexible loops in the enzymatic mechanism and its regulation. Biochemistry. 2002 Aug 6;41(31):9863-72. [Article]
  10. Krajewski WW, Jones TA, Mowbray SL: Structure of Mycobacterium tuberculosis glutamine synthetase in complex with a transition-state mimic provides functional insights. Proc Natl Acad Sci U S A. 2005 Jul 26;102(30):10499-504. Epub 2005 Jul 18. [Article]
  11. Nilsson MT, Krajewski WW, Yellagunda S, Prabhumurthy S, Chamarahally GN, Siddamadappa C, Srinivasa BR, Yahiaoui S, Larhed M, Karlen A, Jones TA, Mowbray SL: Structural basis for the inhibition of Mycobacterium tuberculosis glutamine synthetase by novel ATP-competitive inhibitors. J Mol Biol. 2009 Oct 23;393(2):504-13. doi: 10.1016/j.jmb.2009.08.028. Epub 2009 Aug 18. [Article]
  12. Gising J, Nilsson MT, Odell LR, Yahiaoui S, Lindh M, Iyer H, Sinha AM, Srinivasa BR, Larhed M, Mowbray SL, Karlen A: Trisubstituted imidazoles as Mycobacterium tuberculosis glutamine synthetase inhibitors. J Med Chem. 2012 Mar 22;55(6):2894-8. doi: 10.1021/jm201212h. Epub 2012 Mar 8. [Article]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB04272Citric acidapproved, nutraceutical, vet_approvedunknownDetails