TITLE

Structural characterization of CA1462, the Candida albicans thiamine pyrophosphokinase

AUTHOR(S)
Santini, Sébastien; Monchois, Vincent; Mouz, Nicolas; Sigoillot, Cécile; Rousselle, Tristan; Claverie, Jean-Michel; Abergel, Chantal
PUB. DATE
January 2008
SOURCE
BMC Structural Biology;2008, Vol. 8, Special section p1
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Background: In search of new antifungal targets of potential interest for pharmaceutical companies, we initiated a comparative genomics study to identify the most promising protein-coding genes in fungal genomes. One criterion was the protein sequence conservation between reference pathogenic genomes. A second criterion was that the corresponding gene in Saccharomyces cerevisiae should be essential. Since thiamine pyrophosphate is an essential product involved in a variety of metabolic pathways, proteins responsible for its production satisfied these two criteria. Results: We report the enzymatic characterization and the crystallographic structure of the Candida albicans Thiamine pyrophosphokinase. The protein was co-crystallized with thiamine or thiamine-PNP. Conclusion: The presence of an inorganic phosphate in the crystallographic structure opposite the known AMP binding site relative to the thiamine moiety suggests that a second AMP molecule could be accommodated in the C. albicans structure. Together with the crystallographic structures of the enzyme/substrate complexes this suggests the existence of a secondary, less specific, nucleotide binding site in the Candida albicans thiamine pyrophosphokinase which could transiently serve during the release or the binding of ATP. The structures also highlight a conserved Glutamine residue (Q138) which could interact with the ATP α-phosphate and act as gatekeeper. Finally, the TPK/Thiamine-PNP complex is consistent with a one step mechanism of pyrophosphorylation.
ACCESSION #
35702901

 

Related Articles

  • Predicting phenotype from patterns of annotation. O.D. King; J.C. Lee; A.M. Dudley; D.M. Janse; G.M. Church; F.P. Roth // Bioinformatics;Jan2009 Supplement, Vol. 19, p183 

    Motivation:Predicting the outcome of specific experiments (such as the growth of a particular mutant strain in a particular medium) has the potential to allow researchers to devote resources to experiments with higher expected numbers of 'hits'. Results: We use decision trees to predict...

  • Identification and Phylogenetic Analysis of a Glucose Transporter Gene Family from the Human Pathogenic Yeast Candida albicans. Fan, Jinjiang; Chaturvedi, Vishnu; Shen, Shi-Hsiang // Journal of Molecular Evolution;Sep2002, Vol. 55 Issue 3, p336 

    We have identified a large family of glucose transporter genes (HGT1 to HGT20) from the human pathogenic yeast Candida albicans by screening of genomic sequences, reverse-transcription PCR assays, and phylogenetic analyses. The putative glucose transporter ORF sequences share among themselves...

  • PKC Signaling Regulates Drug Resistance of the Fungal Pathogen Candida albicans via Circuitry Comprised of Mkc1, Calcineurin, and Hsp90.  // PLoS Pathogens;Aug2010, Vol. 6 Issue 8, p1 

    No abstract available.

  • Identification and functional characterization of Candida albicans CDC4. Jia-Ching Shieh; White, Anne; Yu-Che Cheng; Rosamond, John // Journal of Biomedical Science;Nov2005, Vol. 12 Issue 6, p913 

    The CDC4 gene of Saccharomyces cerevisiae encodes an essential function that is required for G1-S and G2-M transitions during mitosis and at various stages during meiosis. We have isolated a functional homologue of CDC4 ( CaCDC4) from the pathogenic yeast Candida albicans by complementing the S....

  • Consistent Patterns of Rate Asymmetry and Gene Loss Indicate Widespread Neofunctionalization of Yeast Genes After Whole-Genome Duplication. Byrne, Kevin P.; Wolfe, Kenneth H. // Genetics;Mar2007, Vol. 175 Issue 3, p1341 

    We investigated patterns of rate asymmetry in sequence evolution among the gene pairs (ohnologs) formed by whole-genome duplication (WGD) in yeast species. By comparing three species (Saccharomyces cerevisiae, Candida glabrata, and S. castellii) that underwent WGD to a nonduplicated outgroup...

  • Amino Acid Metabolic Origin as an Evolutionary Influence on Protein Sequence in Yeast. de Bivort, Benjamin L.; Perlstein, Ethan O.; Kunes, Sam; Schreiber, Stuart L. // Journal of Molecular Evolution;May2009, Vol. 68 Issue 5, p490 

    The metabolic cycle of Saccharomyces cerevisiae consists of alternating oxidative (respiration) and reductive (glycolysis) energy-yielding reactions. The intracellular concentrations of amino acid precursors generated by these reactions oscillate accordingly, attaining maximal concentration...

  • Evolution of Simple Sequence in Proteins. Huntley, Melanie; Golding, G. Brian // Journal of Molecular Evolution;Aug2000, Vol. 51 Issue 2, p131 

    The proteins of Saccharomyces cerevisiae contain a high proportion of low-complexity, simple sequences. These are protein segments composed almost exclusively or largely of a single repetitive amino acid polymer and are the most commonly shared feature between proteins. We have examined a survey...

  • Isolation and characterization of a novel actin filament-binding protein from Saccharomyces cerevisiae. Asakura, Takeshi; Sasaki, Takuya; Nagano, Fumiko; Satoh, Ayako; Obaishi, Hiroshi; Nishioka, Hideo; Imamura, Hiroshi; Hotta, Kazuhiko; Tanaka, Kazuma; Nakanishi, Hiroyuki; Takai, Yoshimi // Oncogene;1/8/98, Vol. 16 Issue 1, p121 

    We purified a novel actin filament (F-actin)-binding protein from the soluble fraction of Saccharomyces cerevisiae by successive column chromatographies by use of the 125I-labeled F-actin blot overlay method. The purified protein showed a minimum Mr of about 140 kDa on SDS-polyacrylamide gel...

  • Meiotic Rec8 cohesins and their mitotic Rad21 orthologs: Comparison in silico. Grishaeva, T.M.; Dadashev, S.Yu.; Bogdanov, Yu.F. // Molecular Biology;Jul2007, Vol. 41 Issue 4, p674 

    The article discusses how the Rec8 proteins such as Rec8 from yeast Sacharromyces cerevisiae, Rec8 proteins from mouse Mus musculus, Rec8L1 from human and variant of 1 of Syn2/Dif1 from thale cress Arabidopsis thaliana, are studied in silico. The similarity between the amino acid sequences of...

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