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Supporting Information High-Throughput Virtual Screening

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Supporting Information High-Throughput Virtual Screening of Proteins using GRID Molecular Interaction Fields Simone Sciabola, Robert V. Stanton, James E. Mills, Maria M. Flocco, Massimo Baroni, Gabriele Cruciani, Francesca Perruccio and Jonathan S. Mason Contents Table S1 S2-S21 Figure S1 S22 * To whom correspondence should be addressed: Simone Sciabola, Pfizer Research Technology Center, Cambridge, 02139 MA, USA Phone: +1-617-551-3327; Fax: +1-617-551-3117; E-mail: [email protected] S1 Table S1. Description of the 990 proteins used as decoy for the Protein Virtual Screening analysis. PDB ID Protein family Molecule Res. (Å) 1n24 ISOMERASE (+)-BORNYL DIPHOSPHATE SYNTHASE 2.3 1g4h HYDROLASE 1,3,4,6-TETRACHLORO-1,4-CYCLOHEXADIENE HYDROLASE 1.8 1cel HYDROLASE(O-GLYCOSYL) 1,4-BETA-D-GLUCAN CELLOBIOHYDROLASE I 1.8 1vyf TRANSPORT PROTEIN 14 KDA FATTY ACID BINDING PROTEIN 1.85 1o9f PROTEIN-BINDING 14-3-3-LIKE PROTEIN C 2.7 1t1s OXIDOREDUCTASE 1-DEOXY-D-XYLULOSE 5-PHOSPHATE REDUCTOISOMERASE 2.4 1t1r OXIDOREDUCTASE 1-DEOXY-D-XYLULOSE 5-PHOSPHATE REDUCTOISOMERASE 2.3 1q0q OXIDOREDUCTASE 1-DEOXY-D-XYLULOSE 5-PHOSPHATE REDUCTOISOMERASE 1.9 1jcy LYASE 2-DEHYDRO-3-DEOXYPHOSPHOOCTONATE ALDOLASE 1.9 1fww LYASE 2-DEHYDRO-3-DEOXYPHOSPHOOCTONATE ALDOLASE 1.85 1uk7 HYDROLASE 2-HYDROXY-6-OXO-7-METHYLOCTA-2,4-DIENOATE 1.7 1v11 OXIDOREDUCTASE 2-OXOISOVALERATE DEHYDROGENASE ALPHA SUBUNIT 1.95 1x7w OXIDOREDUCTASE 2-OXOISOVALERATE DEHYDROGENASE ALPHA SUBUNIT 1.73 1d0l TRANSFERASE 35KD SOLUBLE LYTIC TRANSGLYCOSYLASE 1.97 2bt4 LYASE 3-DEHYDROQUINATE DEHYDRATASE 1.7 2c4w LYASE 3-DEHYDROQUINATE DEHYDRATASE 1.55 1nr5 LYASE 3-DEHYDROQUINATE SYNTHASE 2.1 2gfx TRANSFERASE 3-OXOACYL-[ACYL-CARRIER-PROTEIN] SYNTHASE 2 2.59 1okz TRANSFERASE 3-PHOSPHOINOSITIDE DEPENDENT PROTEIN KINASE 1 2.51 1q36 TRANSFERASE 3-PHOSPHOSHIKIMATE 1-CARBOXYVINYLTRANSFERASE 1.6 2vf3 TRANSFERASE 4-DIPHOSPHOCYTIDYL-2C-METHYL-D-ERYTHRITOL KINASE 2.2 1rr8 ISOMERASE/DNA DNA 2.6 1rrj ISOMERASE/DNA DNA 2.3 1jwl TRANSCRIPTION/DNA DNA 4 1jft TRANSCRIPTION/DNA DNA 2.5 1t8e TRANSFERASE/ELECTRON TRANSPORT/DNA DNA 2.54 1ryr TRANSFERASE/DNA DNA 2.28 1skm TRANSFERASE/DNA DNA 2.2 1k27 TRANSFERASE 5'-DEOXY-5'-METHYLTHIOADENOSINE PHOSPHORYLASE 1.95 1hxa LYASE 5-EPI-ARISTOLOCHENE SYNTHASE 2.32 1rqr TRANSFERASE 5'-FLUORO-5'-DEOXYADENOSINE SYNTHASE 2.67 2c5b TRANSFERASE 5'-FLUORO-5'-DEOXYADENOSINE SYNTHASE 2.4 2c2w TRANSFERASE 5'-FLUORO-5'-DEOXYADENOSINE SYNTHASE 2 1q8a TRANSFERASE 5-METHYLTETRAHYDROFOLATE S-HOMOCYSTEINE 1.7 1u22 TRANSFERASE 5-METHYLTETRAHYDROPTEROYLTRIGLUTAMATE-- 2.65 2qtg HYDROLASE 5'-METHYLTHIOADENOSINE NUCLEOSIDASE 1.84 1jdt TRANSFERASE 5'-METHYLTHIOADENOSINE PHOSPHORYLASE 2 2c97 TRANSFERASE 6,7-DIMETHYL-8-RIBITYLLUMAZINE SYNTHASE 2 1pgq OXIDOREDUCTASE (CHOH(D)-NADP+(A)) 6-PHOSPHOGLUCONATE DEHYDROGENASE 3.17 1mlz TRANSFERASE 7,8-DIAMINO-PELARGONIC ACID AMINOTRANSFERASE 2.15 2g6w TRANSFERASE 8-AMINO-7-OXONONANOATE SYNTHASE 2.14 1gkd HYDROLASE 92 KDA TYPE IV COLLAGENASE 2.1 1t9c TRANSFERASE ACETOLACTATE SYNTHASE, MITOCHONDRIAL 2.34 1t9b TRANSFERASE ACETOLACTATE SYNTHASE, MITOCHONDRIAL 2.2 1gqs HYDROLASE ACETYLCHOLINESTERASE 3 2jey HYDROLASE ACETYLCHOLINESTERASE 2.7 S2 1j07 HYDROLASE ACETYLCHOLINESTERASE 2.35 1jjb HYDROLASE ACETYLCHOLINESTERASE 2.3 1n5r HYDROLASE ACETYLCHOLINESTERASE 2.25 2vu2 TRANSFERASE ACETYL-COA ACETYLTRANSFERASE 2.65 2vu1 TRANSFERASE ACETYL-COA ACETYLTRANSFERASE 1.51 1pg3 LIGASE ACETYL-COA SYNTHETASE 2.3 3b6c TRANSCRIPTION ACTII PROTEIN 2.3 1n5s OXIDOREDUCTASE ACTVA-ORF6 MONOOXYGENASE 1.7 2hu8 HYDROLASE ACYLAMINO-ACID-RELEASING ENZYME 2.4 2a8h HYDROLASE ADAM 17 2.3 2fv9 HYDROLASE ADAM 17 2.02 2ddf HYDROLASE ADAM 17 1.7 1r55 HYDROLASE ADAM 33 1.58 2jih HYDROLASE ADAMTS-1 2.1 2ada HYDROLASE ADENOSINE DEAMINASE 2.4 2i6a TRANSFERASE ADENOSINE KINASE 2.2 3dhy HYDROLASE ADENOSYLHOMOCYSTEINASE 2 1s07 TRANSFERASE ADENOSYLMETHIONINE-8-AMINO-7-OXONONANOATE 2.42 1u0h LYASE ADENYLATE CYCLASE, TYPE V 2.9 1tl7 LYASE ADENYLATE CYCLASE, TYPE V 2.8 1cjk LYASE/LYASE/SIGNALING PROTEIN ADENYLATE CYCLASE, TYPE V 3 1cib LIGASE ADENYLOSUCCINATE SYNTHETASE 2.3 1p9b LIGASE ADENYLOSUCCINATE SYNTHETASE 2 1ab8 LYASE ADENYLYL CYCLASE 2.2 1v8t HYDROLASE ADP-RIBOSE PYROPHOSPHATASE 2.6 1s9d PROTEIN TRANSPORT/EXCHANGE FACTOR ADP-RIBOSYLATION FACTOR 1 1.8 1niv LECTIN AGGLUTININ 3 1jlx LECTIN AGGLUTININ 2.2 1msa LECTIN (AGGLUTININ) AGGLUTININ 2.29 1ugy SUGAR BINDING PROTEIN AGGLUTININ ALPHA CHAIN 2.4 1m9n TRANSFERASE, HYDROLASE AICAR TRANSFORMYLASE-IMP CYCLOHYDROLASE 1.93 1xql ISOMERASE ALANINE RACEMASE 1.8 1ee2 OXIDOREDUCTASE ALCOHOL DEHYDROGENASE 1.54 1s2c OXIDOREDUCTASE ALDO-KETO REDUCTASE FAMILY 1 MEMBER C3 1.8 1ah0 OXIDOREDUCTASE ALDOSE REDUCTASE 2.3 1eko OXIDOREDUCTASE ALDOSE REDUCTASE 2.2 1t40 OXIDOREDUCTASE ALDOSE REDUCTASE 1.8 1az1 OXIDOREDUCTASE ALDOSE REDUCTASE 1.8 2nvd OXIDOREDUCTASE ALDOSE REDUCTASE 1.55 1x97 OXIDOREDUCTASE ALDOSE REDUCTASE 1.4 1kap ZINC METALLOPROTEASE ALKALINE PROTEASE 1.64 1kn1 ELECTRON TRANSPORT ALLOPHYCOCYANIN 2.2 2bxu HYDROLASE ALPHA THROMBIN 2.8 2bvs HYDROLASE ALPHA THROMBIN 1.4 1bhx SERINE PROTEASE ALPHA THROMBIN 2.3 1kyu ENDOCYTOSIS/EXOCYTOSIS ALPHA-ADAPTIN C 1.8 1otj OXIDOREDUCTASE ALPHA-KETOGLUTARATE-DEPENDENT TAURINE 1.9 1nkh TRANSFERASE ACTIVATOR/TRANSFERASE ALPHA-LACTALBUMIN 2 1qw8 HYDROLASE ALPHA-L-ARABINOFURANOSIDASE 1.8 3d50 HYDROLASE ALPHA-MANNOSIDASE 2 1.79 S3 3ddg HYDROLASE ALPHA-MANNOSIDASE 2 1.74 3d52 HYDROLASE ALPHA-MANNOSIDASE 2 1.6 2f1b HYDROLASE ALPHA-MANNOSIDASE II 1.45 2f1a HYDROLASE ALPHA-MANNOSIDASE II 1.45 2f18 HYDROLASE ALPHA-MANNOSIDASE II 1.3 2f7p HYDROLASE ALPHA-MANNOSIDASE II 1.28 1ktc HYDROLASE ALPHA-N-ACETYLGALACTOSAMINIDASE 2.4 1d3t BLOOD CLOTTING ALPHA-THROMBIN 3 1bmn COMPLEX (SERINE PROTEASE/INHIBITOR) ALPHA-THROMBIN 2.8 1bmm COMPLEX (SERINE PROTEASE/INHIBITOR) ALPHA-THROMBIN 2.6 1lhd COMPLEX (SERINE PROTEASE/INHIBITOR) ALPHA-THROMBIN 2.35 1hdt COMPLEX (SERINE PROTEINASE/INHIBITOR) ALPHA-THROMBIN 2.6 1doj HYDROLASE/HYDROLASE INHIBITOR ALPHA-THROMBIN 1.7 1afe COMPLEX (SERINE PROTEASE/INHIBITOR) ALPHA-THROMBIN (SMALL SUBUNIT) 2 1ae8 COMPLEX (SERINE PROTEASE/INHIBITOR) ALPHA-THROMBIN (SMALL SUBUNIT) 2 1hlt COMPLEX(SERINE PROTEINASE/INHIBITOR) ALPHA-THROMBIN (SMALL SUBUNIT) 3 1abj HYDROLASE(SERINE PROTEINASE) ALPHA-THROMBIN (SMALL SUBUNIT) 2.4 1iht HYDROLASE(SERINE PROTEINASE) ALPHA-THROMBIN (SMALL SUBUNIT) 2.1 1ihs HYDROLASE(SERINE PROTEINASE) ALPHA-THROMBIN (SMALL SUBUNIT) 2 1nrr SERINE PROTEINASE/RECEPTOR ALPHA-THROMBIN (SMALL SUBUNIT) 2.4 1oip TRANSPORT ALPHA-TOCOPHEROL TRANSFER PROTEIN 1.95 1f2p HYDROLASE AMINOPEPTIDASE 1.8 1o69 STRUCTURAL GENOMICS, UNKNOWN FUNCTION AMINOTRANSFERASE 1.84 1jgi TRANSFERASE AMYLOSUCRASE 2 1gs4 ANDROGEN RECEPTOR ANDROGEN RECEPTOR 1.95 1j37 HYDROLASE ANGIOTENSIN CONVERTING ENZYME 2.4 1r4l HYDROLASE ANGIOTENSIN I CONVERTING ENZYME 2 3 1um5 IMMUNE SYSTEM ANTIBODY 21H3 L CHAIN 1.6 1a4k IMMUNOGLOBULIN ANTIBODY FAB 2.4 2z92 IMMUNE SYSTEM ANTI-CIGUATOXIN ANTIBODY 10C9 FAB HEAVY CHAIN 2.3 1vpo IMMUNE SYSTEM ANTI-TESTOSTERONE (LIGHT CHAIN) 2.15 1lk6 BLOOD CLOTTING ANTITHROMBIN-III 2.8 2nva LYASE ARGININE DECARBOXYLASE, A207R PROTEIN 1.8 1ls6 TRANSFERASE ARYL SULFOTRANSFERASE 1.9 1w6f TRANSFERASE ARYLAMINE N-ACETYLTRANSFERASE 2.1 1bkg AMINOTRANSFERASE ASPARTATE AMINOTRANSFERASE 2.6 1asd AMINOTRANSFERASE ASPARTATE AMINOTRANSFERASE 2.2 1ajs AMINOTRANSFERASE ASPARTATE AMINOTRANSFERASE 1.6 1toj TRANSFERASE ASPARTATE AMINOTRANSFERASE 1.9 2aat TRANSFERASE(AMINOTRANSFERASE) ASPARTATE AMINOTRANSFERASE 2.8 1aib TRANSFERASE(AMINOTRANSFERASE) ASPARTATE AMINOTRANSFERASE 2.8 1ams TRANSFERASE(AMINOTRANSFERASE) ASPARTATE AMINOTRANSFERASE 2.7 1art TRANSFERASE(AMINOTRANSFERASE) ASPARTATE AMINOTRANSFERASE 1.8 1tu0 HYDROLASE/HYDROLASE REGULATOR ASPARTATE CARBAMOYLTRANSFERASE CATALYTIC CHAIN 2.55 1r0c TRANSFERASE ASPARTATE CARBAMOYLTRANSFERASE CATALYTIC CHAIN 2.37 1at1 TRANSFERASE (CARBAMOYL-P,ASPARTATE) ASPARTATE CARBAMOYLTRANSFERASE, CATALYTIC CHAIN 2.8 1pqp OXIDOREDUCTASE ASPARTATE-SEMIALDEHYDE DEHYDROGENASE 2.06 1g51 LIGASE ASPARTYL-TRNA SYNTHETASE 2.4 1v47 TRANSFERASE ATP SULFURYLASE 2.49 1lel UNKNOWN FUNCTION AVIDIN 2.9 S4 2fhl SUGAR BINDING PROTEIN AVIDIN-RELATED PROTEIN 4/5 1.05 1a6v IMMUNOGLOBULIN B1-8 FV (LIGHT CHAIN) 1.8 2iq6 HYDROLASE BACTERIAL LEUCYL AMINOPEPTIDASE 2 2vsl LIGASE BACULOVIRAL IAP REPEAT-CONTAINING PROTEIN 4 2.1 1xb1 APOPTOSIS BACULOVIRAL IAP REPEAT-CONTAINING PROTEIN 8 2.7 1xb0 APOPTOSIS BACULOVIRAL IAP REPEAT-CONTAINING PROTEIN 8 2.2 1q6z LYASE BENZOYLFORMATE DECARBOXYLASE 1 1fgx TRANSFERASE BETA 1,4 GALACTOSYLTRANSFERASE 2.4 2vt4 RECEPTOR BETA1 ADRENERGIC RECEPTOR 2.7 3d4s MEMBRANE PROTEIN BETA-2 ADRENERGIC RECEPTOR/T4-LYSOZYME CHIMERA 2.8 1fiw HYDROLASE BETA-ACROSIN HEAVY CHAIN 2.1 1r43 HYDROLASE BETA-ALANINE SYNTHASE 2.8 1lq2 HYDROLASE BETA-D-GLUCAN GLUCOHYDROLASE ISOENZYME EXO1 2.7 1jyv HYDROLASE BETA-GALACTOSIDASE 1.75 1jyw HYDROLASE BETA-GALACTOSIDASE 1.55 1e1f GLYCOSIDE HYDROLASE BETA-GLUCOSIDASE 2.6 1e4n GLYCOSIDE HYDROLASE BETA-GLUCOSIDASE 2.1 2cer HYDROLASE BETA-GLUCOSIDASE A 2.29 1np0 HYDROLASE BETA-HEXOSAMINIDASE BETA CHAIN 2.5 1iem HYDROLASE BETA-LACTAMASE 2.3 1kds HYDROLASE BETA-LACTAMASE 2.15 1kvm HYDROLASE BETA-LACTAMASE 2.06 2pu2 HYDROLASE BETA-LACTAMASE 1.86 1ymx HYDROLASE BETA-LACTAMASE CTX-M-9 1.7 1hlk HYDROLASE BETA-LACTAMASE, TYPE II 2.5 1gx8 LIPOCALIN BETA-LACTOGLOBULIN 2.4 2vo5 HYDROLASE BETA-MANNOSIDASE 2.3 1m01 HYDROLASE BETA-N-ACETYLHEXOSAMINIDASE 2.1 1o03 ISOMERASE BETA-PHOSPHOGLUCOMUTASE 1.4 1o3e HYDROLASE BETA-TRYPSIN 1.64 1o2k HYDROLASE BETA-TRYPSIN 1.63 1o3o HYDROLASE BETA-TRYPSIN 1.55 1o34 HYDROLASE BETA-TRYPSIN 1.5 1o2v HYDROLASE BETA-TRYPSIN 1.5 1o2u HYDROLASE
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  • Searching for Novel Targets to Control Wheat Head Blight Disease—I-Protein Identification, 3D Modeling and Virtual Screening

    Searching for Novel Targets to Control Wheat Head Blight Disease—I-Protein Identification, 3D Modeling and Virtual Screening

    Advances in Microbiology, 2016, 6, 811-830 http://www.scirp.org/journal/aim ISSN Online: 2165-3410 ISSN Print: 2165-3402 Searching for Novel Targets to Control Wheat Head Blight Disease—I-Protein Identification, 3D Modeling and Virtual Screening Natália F. Martins1, Emmanuel Bresso1, Roberto C. Togawa1, Martin Urban2, John Antoniw2, Bernard Maigret3, Kim Hammond-Kosack2 1EMBRAPA Recursos Genéticos e Biotecnologia Parque Estação Biológica, Brasília, Brazil 2Department of Plant Biology and Crop Science, Rothamsted Research, Harpenden, UK 3CNRS, LORIA, UMR 7503, Lorraine University, Nancy, France How to cite this paper: Martins, N.F., Abstract Bresso, E., Togawa, R.C., Urban, M., Anto- niw, J., Maigret, B. and Hammond-Kosack, Fusarium head blight (FHB) is a destructive disease of wheat and other cereals. FHB K. (2016) Searching for Novel Targets to occurs in Europe, North America and around the world causing significant losses in Control Wheat Head Blight Disease— production and endangers human and animal health. In this article, we provide the I-Protein Identification, 3D Modeling and strategic steps for the specific target selection for the phytopathogen system wheat- Virtual Screening. Advances in Microbiol- ogy, 6, 811-830. Fusarium graminearum. The economic impact of FHB leads to the need for innova- http://dx.doi.org/10.4236/aim.2016.611079 tion. Currently used fungicides have been shown to be effective over the years, but recently cereal infecting Fusaria have developed resistance. Our work presents a new Received: June 21, 2016 perspective on target selection to allow the development of new fungicides. We de- Accepted: September 11, 2016 veloped an innovative approach combining both genomic analysis and molecular Published: September 14, 2016 modeling to increase the discovery for new chemical compounds with both safety Copyright © 2016 by authors and and low environmental impact.
  • Legionella Genus Genome Provide Multiple, Independent Combinations for Replication in Human Cells

    Legionella Genus Genome Provide Multiple, Independent Combinations for Replication in Human Cells

    Supplemental Material More than 18,000 effectors in the Legionella genus genome provide multiple, independent combinations for replication in human cells Laura Gomez-Valero1,2, Christophe Rusniok1,2, Danielle Carson3, Sonia Mondino1,2, Ana Elena Pérez-Cobas1,2, Monica Rolando1,2, Shivani Pasricha4, Sandra Reuter5+, Jasmin Demirtas1,2, Johannes Crumbach1,2, Stephane Descorps-Declere6, Elizabeth L. Hartland4,7,8, Sophie Jarraud9, Gordon Dougan5, Gunnar N. Schroeder3,10, Gad Frankel3, and Carmen Buchrieser1,2,* Table S1: Legionella strains analyzed in the present study Table S2: Type IV secretion systems predicted in the genomes analyzed Table S3: Eukaryotic like domains identified in the Legionella proteins analyzed Table S4: Small GTPases domains detected in the genus Legionella as defined in the CDD ncbi domain database Table S5: Eukaryotic like proteins detected in the Legionella genomes analyzed in this study Table S6: Aminoacid identity of the Dot/Icm components in Legionella species with respect to orthologous proteins in L. pneumophila Paris Table S7: Distribution of seventeen highly conserved Dot/Icm secreted substrates Table S8: Comparison of the effector reperotoire among strains of the same Legionella species Table S9. Number of Dot/Icm secreted proteins predicted in each strain analyzed Table S10: Replication capacity of the different Legionella species analyzed in this study and collection of literature data on Legionella replication Table S11: Orthologous table for all genes of the 80 analyzed strains based on PanOCT. The orthologoss where defined with the program PanOCT using the parameters previously indicated in material and methods.) Figure S1: Distribution of the genes predicted to encode for the biosynthesis of flagella among all Legionella species.
  • Molecular Models for Shikimate Pathway Enzymes of Xylella Fastidiosa

    Molecular Models for Shikimate Pathway Enzymes of Xylella Fastidiosa

    BBRC Biochemical and Biophysical Research Communications 320 (2004) 979–991 www.elsevier.com/locate/ybbrc Molecular models for shikimate pathway enzymes of Xylella fastidiosa Helen Andrade Arcuri,a,1 Fernanda Canduri,a,d,1 Jose Henrique Pereira,a Nelson Jose Freitas da Silveira,a Joao~ Carlos Camera Jr.,a Jaim Simoes~ de Oliveira,b Luiz Augusto Basso,b Mario Sergio Palma,c,d Diogenes Santiago Santos,e,* and Walter Filgueira de Azevedo Jr.a,d,* a Department of Physics IBILCE/UNESP, S~ao Jose do Rio Preto, SP 15054-000, Brazil b Rede Brasileira de Pesquisas em Tuberculose, Department of Molecular Biology and Biotecnology, UFRGS, Porto Alegre, RS 91501-970, Brazil c Laboratory of Structural Biology and Zoochemistry, Department of Biology, Institute of Biosciences, UNESP, Rio Claro, SP 13506-900, Brazil d Center for Applied Toxicology, Institute Butantan, S~ao Paulo, SP 05503-900, Brazil e Center for Research and Development in Molecular, Structural and Functional Molecular Biology, PUCRS 90619-900, Porto Alegre, RS, Brazil Received 25 May 2004 Available online 25 June 2004 Abstract The Xylella fastidiosa is a bacterium that is the cause of citrus variegated chlorosis (CVC). The shikimate pathway is of pivotal importance for production of a plethora of aromatic compounds in plants, bacteria, and fungi. Putative structural differences in the enzymes from the shikimate pathway, between the proteins of bacterial origin and those of plants, could be used for the development of a drug for the control of CVC. However, inhibitors for shikimate pathway enzymes should have high specificity for X. fastidiosa enzymes, since they are also present in plants.
  • United States Patent (19) (11 Patent Number: 4,971,908 Kishore Et Al

    United States Patent (19) (11 Patent Number: 4,971,908 Kishore Et Al

    United States Patent (19) (11 Patent Number: 4,971,908 Kishore et al. 45 Date of Patent: Nov. 20, 1990 54 GLYPHOSATE-TOLERANT 56 References Cited 5-ENOLPYRUVYL-3-PHOSPHOSHKMATE U.S. PATENT DOCUMENTS SYNTHASE 4,769,061 9/1988 Comai ..................................... 71/86 (75. Inventors: Ganesh M. Kishore, Chesterfield; Primary Examiner-Robin Teskin Dilip M. Shah, Creve Coeur, both of Assistant Examiner-S. L. Nolan Mo. Attorney, Agent, or Firm-Dennis R. Hoerner, Jr.; 73 Assignee: Monsanto Company, St. Louis, Mo. Howard C. Stanley; Thomas P. McBride (21) Appl. No.: 179,245 57 ABSTRACT Glyphosate-tolerant 5-enolpyruvyl-3-phosphosikimate 22 Filed: Apr. 22, 1988 (EPSP) synthases, DNA encoding glyhphosate-tolerant EPSP synthases, plant genes encoding the glyphosate Related U.S. Application Data tolerant enzymes, plant transformation vectors contain ing the genes, transformed plant cells and differentiated 63 Continuation-in-part of Ser. No. 54,337, May 26, 1987, transformed plants containing the plant genes are dis abandoned. closed. The glyphosate-tolerant EPSP synthases are 51) Int. Cl. ....................... C12N 15/00; C12N 9/10; prepared by substituting an alanine residue for a glycine CO7H 21/04 residue in a conserved sequence found between posi 52 U.S. C. .............................. 435/172.1; 435/172.3; tions 80 and 120 in the mature wild-type EPSP syn 435/193; 536/27; 935/14 thase. 58) Field of Search............... 435/172.3, 193; 935/14, 935/67, 64 15 Claims, 14 Drawing Sheets U.S. Patent Nov. 20, 1990 Sheet 3 of 14 4,971,908 1. 50 Yeast . .TVYPFK DIPADQQKVV IPPGSKSSN RALITAATGE GQCKIKNLLH Aspergillus .
  • Lllllllllllllllllillllllllllllllilllllllllillllillllllllllll

    Lllllllllllllllllillllllllllllllilllllllllillllillllllllllll

    lllllllllllllllllIllllllllllllllIlllllllllIllllIllllllllllllllllllIllllllll U USOO53 10667A Umted States Patent [19] [11] Patent Number: 5,310,667 Eichholtz et a1. [45] Date of Patent: May 10, 1994 [54] GLYPHOSATE-TOLERANT 5-ENOLPYRUVYL-3-PHOSPHOSHIKIMATE OTHER PUBLICATIONS SYNTHASES Botterman et a1. (Aug. 1988) Trends in Genetics 4:219-222. [75] Inventors: David A_ Eichholtz, St Louis; Dassarma et al. (1986) Science 232:1242-1244. Charles S_ Gasser; Ganesh M_ Oxtoby et al. (1989) Euphytiza 40:173-180. Kishore, both of Chesterfield, an of Sezel, Enzyme Kineties, Behavior and Analysis of Rapid Mo_ Equilibrium and Steady State Enzyme System, John Wiley and Sons, New York, 1975, p. 15. [73] Assignee: Monsanto Company, St. Louis, Mo. Primary Examiner—Che S. Chereskiin Attorney, Agent, or Firm-Dennis R. Hoemer, Jr.; [21] Appl. No.: 380,963 RiChard H- Shear [57] ABSTRACT [22] Filed: Jul- 17’ 1989 Glyphosate-tolerant 5-enolpyruvy1-3-phosphoshikimate (EPSP) synthases, DNA encoding glyphosate-tolerant [51] Int. Cl.5 .................... .. C12N 15/01; C12N 15/29; EPSP synthases, plant genes encoding the glyphosate C12N 15/32 tolerant enzymes, plant transformation vectors contain [52] US. Cl. .............................. .. 435/ 172.3; 435/691; ing the genes, transformed plant cells and differentiated 800/205; 935/30; 935/35; 935/64; 536/236; transformed plants containing the plant genes are dis 536/23.7 closed. The glyphosate-tolerant EPSP synthases are [58] Field of Search ................... .. 435/68, 172.3, 69.1; prepared by substituting an alanine residue for a glycine 935/30, 35, 64, 67; 71/86, 113, 121; 530/370, residue in a ?rst conserved sequence found between 350; 800/205; 536/236, 23.7 positions 80 and 120, and either an aspartic acid residue ‘ or asparagine residue for a glycine residue in a second [56] References Cited conserved sequence found between positions 120 and 160 in the mature wild type EPSP synthase.