title: Functional relevance of dynamic properties of Dimeric NADP-dependent Isocitrate Dehydrogenases.
abstract: BACKGROUND
  Isocitrate Dehydrogenases (IDHs) are important enzymes present in all living cells. Three subfamilies of functionally dimeric IDHs (subfamilies I, II, III) are known. Subfamily I are well-studied bacterial IDHs, like that of Escherischia coli. Subfamily II has predominantly eukaryotic members, but it also has several bacterial members, many being pathogens or endosymbionts. subfamily III IDHs are NAD-dependent. The eukaryotic-like subfamily II IDH from pathogenic bacteria such as Mycobacterium tuberculosis IDH1 are expected to have regulation similar to that of bacteria which use the glyoxylate bypass to survive starvation. Yet they are structurally different from IDHs of subfamily I, such as the E. coli IDH.
  
  
  RESULTS
  We have used phylogeny, structural comparisons and molecular dynamics simulations to highlight the similarity and differences between NADP-dependent dimeric IDHs with an emphasis on regulation. Our phylogenetic study indicates that an additional subfamily (IV) may also be present. Variation in sequence and structure in an aligned region may indicate functional importance concerning regulation in bacterial subfamily I IDHs. Correlation in movement of prominent loops seen from molecular dynamics may explain the adaptability and diversity of the predominantly eukaryotic subfamily II IDHs.
  
  
  CONCLUSIONS
  This study discusses possible regulatory mechanisms operating in various IDHs and implications for regulation of eukaryotic-like bacterial IDHs such as that of M. tuberculosis, which may provide avenues for intervention in disease.
authors.affiliation: School of Computational and Integrative Sciences, Jawaharlal Nehru University, New Mehrauli Road, New Delhi 110067, India.
authors.forename: Rithvik
authors.initials: R
authors.lastname: Vinekar
authors.forename: Chandra
authors.initials: C
authors.lastname: Verma
authors.forename: Indira
authors.initials: I
authors.lastname: Ghosh
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry* / Q000145:classification / Q000235:genetics; D004926:Escherichia coli / Q000201:enzymology; D007521:Isocitrate Dehydrogenase / Q000737:chemistry* / Q000145:classification / Q000235:genetics; D008969:Molecular Sequence Data; D009169:Mycobacterium tuberculosis / Q000201:enzymology; D010802:Phylogeny; D011487:Protein Conformation; D055503:Protein Multimerization; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
chemical_list: D001426:Bacterial Proteins; D007521:Isocitrate Dehydrogenase; C039355:isocitrate dehydrogenase (NADP+)