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Gene Review

icl1  -  isocitrate lyase

Mycobacterium tuberculosis H37Rv

 
 
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Disease relevance of icl

  • Dual role of isocitrate lyase 1 in the glyoxylate and methylcitrate cycles in Mycobacterium tuberculosis [1].
  • It matches a sequence in the M. tuberculosis database (Sanger) with similarity to the enzyme isocitrate lyase of both Corynebacterium glutamicum and Rhodococcus fascians [2].
 

High impact information on icl

  • A link between the requirement for ICL and the immune status of the host was established by the restored virulence of delta icl bacteria in interferon-gamma knockout mice [3].
  • The role of isocitrate lyase (ICL) in the glyoxylate cycle and its necessity for persistence and virulence of Mycobacterium tuberculosis has been well described [1].
  • Only marginal similarity was observed between this open reading frame (ORF) (termed icl) and a second distinct ORF (named aceA) which exhibits a low similarity to other isocitrate lyases [2].
  • Furthermore, we present evidence that in both M. avium and M. tuberculosis the production and activity of the isocitrate lyase is enhanced under minimal growth conditions when supplemented with acetate or palmitate [2].
  • The apparent conservation of certain detailed structural characteristics suggests that KPHMT is distantly related by divergent evolution to enzymes in unrelated pathways, including isocitrate lyase and phosphoenolpyruvate mutase [4].
 

Biological context of icl

  • Disruption of the icl gene attenuated bacterial persistence and virulence in immune-competent mice without affecting bacterial growth during the acute phase of infection [3].
 

Associations of icl with chemical compounds

  • Isocitrate lyase is a key enzyme in the glyoxylate cycle and is essential as an anapleurotic enzyme for growth on acetate and certain fatty acids as carbon source [2].

References

  1. Dual role of isocitrate lyase 1 in the glyoxylate and methylcitrate cycles in Mycobacterium tuberculosis. Gould, T.A., van de Langemheen, H., Muñoz-Elías, E.J., McKinney, J.D., Sacchettini, J.C. Mol. Microbiol. (2006) [Pubmed]
  2. Characterization of activity and expression of isocitrate lyase in Mycobacterium avium and Mycobacterium tuberculosis. Höner Zu Bentrup, K., Miczak, A., Swenson, D.L., Russell, D.G. J. Bacteriol. (1999) [Pubmed]
  3. Persistence of Mycobacterium tuberculosis in macrophages and mice requires the glyoxylate shunt enzyme isocitrate lyase. McKinney, J.D., Höner zu Bentrup, K., Muñoz-Elías, E.J., Miczak, A., Chen, B., Chan, W.T., Swenson, D., Sacchettini, J.C., Jacobs, W.R., Russell, D.G. Nature (2000) [Pubmed]
  4. The crystal structure of the first enzyme in the pantothenate biosynthetic pathway, ketopantoate hydroxymethyltransferase, from M tuberculosis. Chaudhuri, B.N., Sawaya, M.R., Kim, C.Y., Waldo, G.S., Park, M.S., Terwilliger, T.C., Yeates, T.O. Structure (Camb.) (2003) [Pubmed]
 
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