24121-00-4Relevant academic research and scientific papers
Identification of critical ligand binding determinants in Mycobacterium tuberculosis adenosine-5′-phosphosulfate reductase
Hong, Jiyoung A.,Bhave, Devayani P.,Carroll, Kate S.
, p. 5485 - 5495 (2009)
Mycobacterium tuberculosis adenosine-5′-phosphosulfate (APS) reductase is an iron-sulfur protein and a validated target to develop new antitubercular agents, particularly for the treatment of latent infection. To facilitate the development of potent and specific inhibitors of APS reductase, we have probed the molecular determinants that underlie binding and specificity through a series of substrate and product analogues. Our study highlights the importance of specific substitutent groups for substrate binding and provides functional evidence for ligand-specific conformational states. An active site model has been developed for M. tuberculosis APS reductase that is in accord with the results presented here as well as prior structural data reported for Pseudomonas aeruginosa APS reductase and related enzymes. This model illustrates the functional features required for the interaction of APS reductase with a ligand and provides a pharmacological roadmap for the rational design of small molecules as potential inhibitors of APS reductase present in human pathogens, including M. tuberculosis.
cADPR Analogues: Effect of an Adenosine 2′- Or 3′-Methoxy Group on Conformation
Graham, Steven M.,Macaya, Daniel J.,Sengupta, Raghuvir N.,Turner, Kevin B.
, p. 233 - 236 (2007/10/03)
(Matrix presented) The 2′-OMe-A (2) and 3′-OMe-A (3) analogues of the calcium release agent cADPR (1) were prepared and their solution structures studied by NMR spectroscopy. Compared to 1, 2 shows a shift in its A ring conformation and changes in its R ring N:S and γt: γ+ ratios, while 3 displays a significant change in the conformation of its A ring γ-bond.
