TITLE

Cation induced differential effect on structural and functional properties of Mycobacterium tuberculosis α-Isopropylmalate synthase

AUTHOR(S)
Singh, Kulwant; Bhakuni, Vinod
PUB. DATE
January 2007
SOURCE
BMC Structural Biology;2007, Vol. 7, p1
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Background: α-isopropylmalate synthase (MtαIPMS), an enzyme that catalyzes the first committed step of the leucine biosynthetic pathway of Mycobacterium tuberculosis is a potential drug target for the anti-tuberculosis drugs. Cations induce differential effect of activation and inhibition of MtαIPMS. To date no concrete mechanism for such an opposite effect of similarly charged cations on the functional activity of enzyme has been presented. Results: Effect of cations on the structure and function of the MtαIPMS has been studied in detail. The studies for the first time demonstrate that different cations interact specifically at different sites in the enzyme and modulate the enzyme structure differentially. The inhibitors Zn2+ and Cd2+ ions interact directly with the catalytic domain of the enzyme and induce unfolding/denaturation of the domain. The activator K+ also interacts with the catalytic TIM barrel domain however, it does not induce any significant effect on the enzyme structure. Studies with isolated catalytic TIM barrel domain showed that it can carry out the catalytic function on its own but probably requires the non-catalytic C-terminal domain for optimum functioning. An important observation was that divalent cations induce significant interaction between the regulatory and the catalytic domain of MtαIPMS thus inducing structural cooperativity in the enzyme. This divalent cation induced structural cooperativity might result in modulation of activity of the catalytic domain by regulatory domain. Conclusion: The studies for the first time demonstrate that different cations bind at different sites in the enzyme leading to their differential effects on the structure and functional activity of the enzyme.
ACCESSION #
29323597

 

Related Articles

  • Heterotropic Cooperativity in Oxidation Mediated by Cytochrome P450. Niwa, Toshiro; Murayama, Norie; Yamazaki, Hiroshi // Current Drug Metabolism;Jun2008, Vol. 9 Issue 5, p453 

    Cytochrome P450s (P450 or CYPs) comprise a superfamily of enzymes that catalyze the oxidation of a wide variety of xenobiotic chemicals. Although most of P450 inhibitors decrease the metabolic activities mediated by the corresponding P450 forms, unexpected phenomena, which are called as...

  • Cooperative Binding of l-Trp to Human Tryptophan 2,3-Dioxygenase: Resonance Raman Spectroscopic Analysis. Fukumura, Eiko; Hiroshi, Sugimoto; Misumi, Yuko; Ogura, Takashi; Shiro, Yoshitsugu // Journal of Biochemistry;Apr2009, Vol. 145 Issue 4, p505 

    Tryptophan 2,3-dioxygenase (TDO) is a tetrameric enzyme that catalyses the oxidative cleavage of l-tryptophan (l-Trp) to N-formylkynurenine by the addition of O2 across the 2,3-bond of the indole ring. This reaction is the first and rate-limiting step in the kynurenine pathway in mammals. In the...

  • Two In One. Hobbs, Heather // International Labmate;2011, Vol. 36 Issue 2, p2 

    The article reports on the findings of a study conducted by the group of Matthias Wilmanns at the European Molecular Biology Laboratory (EMBL) in Germany on an enzyme from Mycobacterium tuberculosis.

  • Dynamic Disorder in Quasi-Equilibrium Enzymatic Systems. Chaudhury, Srabanti; Igoshin, Oleg A. // PLoS ONE;2010, Vol. 5 Issue 8, p1 

    Conformations and catalytic rates of enzymes fluctuate over a wide range of timescales. Despite these fluctuations, there exist some limiting cases in which the enzymatic catalytic rate follows the macroscopic rate equation such as the Michaelis- Menten law. In this paper we investigate the...

  • Cooperativity in ionic liquids. Koßmann, Simone; Thar, Jens; Kirchner, Barbara; Hunt, Patricia A.; Welton, Tom // Journal of Chemical Physics;5/7/2006, Vol. 124 Issue 17, p174506 

    Cooperativity in ionic liquids is investigated by means of static quantum chemical calculations. Larger clusters of the dimethylimidazolium cation paired with a chloride anion are calculated within density functional theory combined with gradient corrected functionals. Tests of the monomer unit...

  • Entropic estimate of cooperative binding of substrate on a single oligomeric enzyme: An index of cooperativity. Banerjee, Kinshuk; Das, Biswajit; Gangopadhyay, Gautam // Journal of Chemical Physics;4/12/2012, Vol. 136 Issue 15, p154502 

    Here we have systematically studied the cooperative binding of substrate molecules on the active sites of a single oligomeric enzyme in a chemiostatic condition. The average number of bound substrate and the net velocity of the enzyme catalyzed reaction are studied by the formulation of...

  • Production and Purification of Mycolyl Transferase B of Mycobacterium tuberculosis. Aghababa, Haniyeh; Mobarez, Ashraf Mohabati; Behmanesh, Mehrdad; Khoramabadi, Nima; Mobarhan, Mandana // Tanaffos;2011, Vol. 10 Issue 4, p23 

    Background: Antigen 85 complex of Mycobacterium tuberculosis includes three immunogenic proteins which are TB vaccine candidates of great importance. As they are very hard to be achieved in natural form, recombinant production of them fuels immunological experiments. Production of such apolar...

  • Kinetic properties of Mycobacterium tuberculosis bifunctional GlmU. Yan Zhou; Yi Xin; Shanshan Sha; Yufang Ma // Archives of Microbiology;Oct2011, Vol. 193 Issue 10, p751 

    The UDP-N-acetylglucosamine (UDP-GlcNAc) is present as one of the glycosyl donors for disaccharide linker ( d-N-GlcNAc- l-rhamnose) and the precursor of peptidoglycan in mycobacteria. The bifunctional enzyme GlmU involves in the last two sequential steps of UDP-GlcNAc synthetic pathway....

  • Uptake of unnatural trehalose analogs as a reporter for Mycobacterium tuberculosis. Backus, Keriann M.; Boshoff, Helena I.; Barry, Conor S.; Boutureira, Omar; Patel, Mitul K.; D'Hooge, François; Lee, Seung Seo; Via, Laura E.; Tahlan, Kapil; Barry, Clifton E.; Davis, Benjamin G. // Nature Chemical Biology;Apr2011, Vol. 7 Issue 4, p228 

    The detection of tuberculosis currently relies upon insensitive and unspecific techniques; newer diagnostics would ideally co-opt specific bacterial processes to provide real-time readouts. The trehalose mycolyltransesterase enzymes (antigens 85A, 85B and 85C (Ag85A, Ag85B, Ag85C)) serve as...

Share

Read the Article

Courtesy of VIRGINIA BEACH PUBLIC LIBRARY AND SYSTEM

Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics