Asparagine synthetase

from Wikipedia, the free encyclopedia
Asparagine synthetase
other names

Cell cycle control protein TS11

Properties of human protein
Mass / length primary structure 54.8 to 64.4 kDa / 478 to 561 amino acids (depending on isoform)
Isoforms 3
Identifier
Gene names ASNS TS11
External IDs
Enzyme classification
EC, category 6.3.5.4 ,  ligase
Response type Amination
Substrate ATP + L -aspartate + L -glutamine + H 2 O
Products AMP + PP i + L -asparagine + L -glutamate
Occurrence
Homology family Asparagine synthetase
Parent taxon Creature
Orthologue
human House mouse
Entrez 440 27053
Ensemble ENSG00000070669 ENSMUSG00000029752
UniProt P08243 Q61024
Refseq (mRNA) NM_001178075 NM_012055
Refseq (protein) NP_001171546 NP_036185
Gene locus Chr 7: 97.85 - 97.87 Mb Chr 6: 7.68 - 7.69 Mb
PubMed search 440 27053

Asparagine synthetase (ASNS) is an enzyme found in all living things . It catalyzes the body's own production of the amino acid L- asparagine from L- aspartate and L- glutamine .

The enzyme consists of two domains: the part that removes the amino group from glutamine (glutamine amidotransferase, EC  2.4.2.- ); the amino group is channeled as ammonium to the C-terminal end of the enzyme, where aspartate is prepared as β-aspartyl-AMP and finally the amination and separation of AMP takes place.

The catalyzed reaction equilibrium is:

L-Asp+ L -glutamine + ATP + H 2 O ⇔
⇔ L-Asn+ L -glutamate + AMP + PP i

The reverse reaction can win adenosine triphosphate when asparagine is consumed and becomes active when there is an extreme glucose deficiency, which triggers the increased production of the enzyme. ASNS production is also ramped up in the event of an asparagine deficiency - the transcription factors ATF5 and CHOP play a role here.

Acute lymphoblastic leukemia is combated , among other things, by artificially generated asparagine deficiency with the help of asparaginase . Resistance to this treatment is due to the activity of the ASNS. In order to make this resistance treatable, increasing efforts are being made to find ASNS inhibitors.

Individual evidence

  1. ↑ UniProt P08243
  2. ↑ Swiss Institute of Bioinformatics (SIB): PROSITE documentation PDOC00406. Retrieved August 10, 2011 .
  3. ↑ Cui H, Darmanin S, Natsuisaka M, et al : Enhanced expression of asparagine synthetase under glucose-deprived conditions protects pancreatic cancer cells from apoptosis induced by glucose deprivation and cisplatin . In: Cancer Res . 67, No. 7, April 2007, pp. 3345-55. doi : 10.1158 / 0008-5472.CAN-06-2519 . PMID 17409444 .
  4. ↑ Al Sarraj J, Vinson C, Thiel G: Regulation of asparagine synthetase gene transcription by the basic region leucine zipper transcription factors ATF5 and CHOP . In: Biol. Chem. . 386, No. 9, September 2005, pp. 873-9. doi : 10.1515 / BC.2005.102 . PMID 16164412 .
  5. ↑ Richards NG, Kilberg MS: asparagine synthetase chemotherapy . In: Annu. Rev. Biochem. . 75, 2006, pp. 629-54. doi : 10.1146 / annurev.biochem.75.103004.142520 . PMID 16756505 .
  6. ↑ Gutierrez JA, Pan YX, Koroniak L, Hiratake J, Kilberg MS, Richards NG: An inhibitor of human asparagine synthetase suppresses proliferation of an L-asparaginase-resistant leukemia cell line . In: Chem Biol.. . 13, No. 12, December 2006, pp. 1339-47. doi : 10.1016 / j.chembiol.2006.10.010 . PMID 17185229 .

Web links

Wikibooks: Biochemistry and Pathobiochemistry: Asparagine Synthase (Glutamine Hydrolyzing)  - Learning and Teaching Materials