Shaping development of autophagy inhibitors with the structure of the lipid kinase Vps34

Science

Volumn 327, Issue 5973, 2010, Pages 1638-1642

  Miller, Simon ^a   Tavshanjian, Brandon ^b   Oleksy, Arkadiusz ^a   Perisic, Olga ^a   Houseman, Benjamin T ^b   Shokat, Kevan M ^b   Williams, Roger L ^a  

^a MRC LABORATORY OF MOLECULAR BIOLOGY   (United Kingdom)

^b UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ADENINE; ADENOSINE TRIPHOSPHATASE; ENZYME; PHOSPHATIDYLINOSITOL 3 KINASE; UNCLASSIFIED DRUG; VPS34 KINASE;

CRYSTAL; ENZYME; EUKARYOTE; HEALTH AND SAFETY; INHIBITOR; LIPID; SIGNALING;

ARTICLE; AUTOPHAGY; CARBOXY TERMINAL SEQUENCE; CATALYSIS; CRYSTAL STRUCTURE; CYTOSOL; ENZYME ANALYSIS; ENZYME DEGRADATION; ENZYME STRUCTURE; MEMBRANE; NONHUMAN; PRIORITY JOURNAL; STRUCTURE ANALYSIS;

1-PHOSPHATIDYLINOSITOL 3-KINASE; ADENINE; ADENOSINE TRIPHOSPHATASES; ANIMALS; AUTOPHAGY; BINDING SITES; CATALYSIS; CATALYTIC DOMAIN; CELL MEMBRANE; CRYSTALLOGRAPHY, X-RAY; DROSOPHILA MELANOGASTER; DROSOPHILA PROTEINS; ENZYME INHIBITORS; FURANS; HUMANS; HYDROPHOBICITY; MODELS, MOLECULAR; PHOSPHATIDYLINOSITOLS; POINT MUTATION; PROTEIN CONFORMATION; PROTEIN STRUCTURE, SECONDARY; PROTEIN STRUCTURE, TERTIARY; PYRIDINES; PYRIMIDINES;

EUKARYOTA;

EID: 77950212231     PISSN: 00368075     EISSN: 10959203     Source Type: Journal    
DOI: 10.1126/science.1184429     Document Type: Article

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30. Single-letter abbreviations for the amino acid residues are as follows: A, Ala; C, Cys; D, Asp; E, Glu; F, Phe; G, Gly; H, His; I, lle; K, Lys; L, Leu; M, Met; N, Asn; P, Pro; Q, Gln; R, Arg; S, Ser; T, Thr; V, Val; W, Trp; and Y, Tyr.
31. We thank European Synchrotron Radiation Facility beamline scientists for ID14-4, ID23-1, and ID29. We are grateful to Y. Ohashi and A. Gillingham for help with yeast experiments, C. Sachse for electron microscopy, M. Allen for help with x-ray data collection, A. Berndt for advice and discussions, S. Munro for critically reading the manuscript, B. González for a clone of HsVps34, and G. Ducker for help in optimizing Vps34 inhibitor assays. B.T.H. is supported by the Mount Zion Health Fund, BI. is supported by the Achievement Rewards for College Scientists Fellowship at UCSF, and K.M.S. thanks the Waxman Foundation for support. The coordinates have been deposited in the Protein Data Bank, with the following identification numbers (PDB IDs): 2X6H (apo), 2X61 (PIK-90), 2X6] (PIK-93), 2X6K (PI-103), and 2X6F (3-MA).