The Structural Comparison Between Membrane-Associated Human Carbonic Anhydrases Provides Insights Into Drug Design Of Selective Inhibitors(546 views) Alterio V, Pan P, Parkkila S, Buonanno M, Supuran CT, Monti SM, De Simone G
Keywords: Carbonic Anhydrase, Drug Design, Inhibitors, X-Ray Crystallography, Corrosion Inhibitors, Drug Delivery, Enzyme Inhibition, X Ray Crystallography, Crystallographic Structure, Extracellular Domains, Human Carbonic Anhydrases, Membrane-Associated Proteins, Structural Comparison, Structural Differences, Transmembrane Regions, Carbonate Dehydratase, Carbonate Dehydratase Inhibitor, Carbonate Dehydratase Xii, Unclassified Drug, Article, Controlled Study, Crystal Structure, Enzyme Purification, Enzyme Structure, Molecule, Protein Expression, Sequence Alignment,
Affiliations: *** IBB - CNR ***
Institute of Biostructures and Bioimaging, CNR, Via Mezzocannone 16, 80134 Naples, Italy
Institute of Biomedical Technology, University of Tampere, Tampere University Hospital, FI-33014 Tampere, Finland
Laboratory of Bioinorganic Chemistry, Department of Chemistry, University of Florence, Via della Lastruccia 3, 50019 Sesto Fiorentino (Florence), Italy
Section of Pharmaceutical Chemistry, NEUROFARBA Department, Via Ugo Schiff 6, 50019 Sesto Fiorentino (Florence), Italy
References: Not available.
The Structural Comparison Between Membrane-Associated Human Carbonic Anhydrases Provides Insights Into Drug Design Of Selective Inhibitors
Carbonic anhydrase isoform XIV (CA XIV) is the last member of the human (h) CA family discovered so far, being localized in brain, kidneys, colon, small intestine, urinary bladder, liver, and spinal cord. It has recently been described as a possible drug target for treatment of epilepsy, some retinopathies as well as some skin tumors. Human carbonic anhydrase (hCA) XIV is a membrane-associated protein consisting of an N-terminal extracellular domain, a putative transmembrane region, and a small cytoplasmic tail. In this article, we report the expression, purification, and the crystallographic structure of the entire extracellular domain of this enzyme. The analysis of the structure revealed the typical alpha-CA fold, in which a 10-stranded beta-sheet forms the core of the molecule, while the comparison with all the other membrane associated isoforms (hCAs IV, IX, and XII) allowed to identify the diverse oligomeric arrangement and the sequence and structural differences observed in the region 127-136 as the main factors to consider in the design of selective inhibitors for each one of the membrane associated alpha-CAs. (c) 2013 Wiley Periodicals, Inc. Biopolymers 101: 769-778, 2014
The Structural Comparison Between Membrane-Associated Human Carbonic Anhydrases Provides Insights Into Drug Design Of Selective Inhibitors
Kim YH, Shin SW, Pellicano R, Fagoonee S, Choi IJ, Kim YI, Park B, Choi JM, Kim SG, Choi J, Park JY, Oh S, Yang HJ, Lim JH, Im JP, Kim JS, Jung HC, Ponzetto A, Figura N, Malfertheiner P, Choi IJ, Kook MC, Kim YI, Cho SJ, Lee JY, Kim CG, Park B, Nam BH, Bae SE, Choi KD, Choe J, Kim SO, Na HK, Choi JY, Ahn JY, Jung KW, Lee J, Kim DH, Chang HS, Song HJ, Lee GH, Jung HY, Seta T, Takahashi Y, Noguchi Y, Shikata S, Sakai T, Sakai K, Yamashita Y, Nakayama T, Leja M, Park JY, Murillo R, Liepniece-karele I, Isajevs S, Kikuste I, Rudzite D, Krike P, Parshutin S, Polaka I, Kirsners A, Santare D, Folkmanis V, Daugule I, Plummer M, Herrero R, Tsukamoto T, Nakagawa M, Kiriyama Y, Toyoda T, Cao X, Corral JE, Mera R, Dye CW, Morgan DR, Lee YC, Lin JT, Garcia Martin R, Matia Cubillo A, Lee SH, Park JM, Han YM, Ko WJ, Hahm KB, Leontiadis GI, Ford AC, Ichinose M, Sugano K, Jeong M, Park JM, Han YM, Park KY, Lee DH, Yoo JH, Cho JY, Hahm KB, Bang CS, Baik GH, Shin IS, Kim JB, Suk KT, Yoon JH, Kim YS, Kim DJ * Helicobacter pylori Eradication for Prevention of Metachronous Recurrence after Endoscopic Resection of Early Gastric Cancer(667 views) N Engl J Med (ISSN: 0028-4793, 0028-4793linking, 1533-4406electronic), 2015 Jun; 30642104201566393291: 749-756. Impact Factor:59.558 ViewExport to BibTeXExport to EndNote