Title:
CRYSTAL STRUCTURE INFORMATION OF PNP SYNTHASE AND THE USE THEREOF
Document Type and Number:
WIPO Patent Application WO2002068622
Kind Code:
A3
Abstract:
The present invention relates to crystal structure information obtained from crystalline preparations of pyridoxine 5'-phosphate (PNP) synthase (PdxJ) and its use for the design of active site PNP synthase mutants and for the design and/or identification of inhibitors of PNP synthase. A further subject matter of the invention are PNP inhibitor molecules and their use in pharmaceutical compositions for the treatment and/or prevention of diseases caused by pathogens containing PNP synthase.
Inventors:
FRANCO MARTA GARRIDO (DE)
HUBER ROBERT (DE)
CLAUSEN TIM (DE)
HUBER ROBERT (DE)
CLAUSEN TIM (DE)
Application Number:
PCT/EP2002/001897
Publication Date:
December 24, 2003
Filing Date:
February 22, 2002
Export Citation:
Assignee:
MAX PLANCK GESELLSCHAFT (DE)
FRANCO MARTA GARRIDO (DE)
HUBER ROBERT (DE)
CLAUSEN TIM (DE)
FRANCO MARTA GARRIDO (DE)
HUBER ROBERT (DE)
CLAUSEN TIM (DE)
International Classes:
C12N9/88; (IPC1-7): C12N9/10; A61K38/00; G06F17/50
Other References:
FRANCO M G ET AL: "CRYSTALLIZATION AND PRELIMINARY X-RAY CRYSTALLOGRAPHIC ANALYSIS OF PDXJ, THE PYRIDOXINE 5'-PHOSPHATE SYNTHESIZING ENZYME", ACTA CRYSTALLOGRAPHICA SECTION D: BIOLOGICAL CHRYSTALLOGRAPHY,MUNKSGAARD PUBLISHERS LTD. COPENHAGEN,DK, vol. D56, no. 8, August 2000 (2000-08-01), pages 1045 - 1048, XP001005210, ISSN: 0907-4449
LABER BERND ET AL: "Vitamin B6 biosynthesis: Formation of pyridoxine 5'-phosphate from 4-(phosphohydroxy)-L-threonine and 1-deoxy-D-xylulose-5-phosphate by PdxA and PdxJ protein.", FEBS LETTERS, vol. 449, no. 1, 16 April 1999 (1999-04-16), pages 45 - 48, XP000999499, ISSN: 0014-5793
BAMBOROUGH P ET AL: "MODELING PROTEIN-LIGAND COMPLEXES", CURRENT OPINION IN STRUCTURAL BIOLOGY,CURRENT BIOLOGY LTD., LONDON,GB, vol. 6, no. 2, April 1996 (1996-04-01), pages 236 - 241, XP001005308, ISSN: 0959-440X
LYBRAND T P: "LIGAND-PROTEIN DOCKING AND RATIONAL DRUG DESIGN", CURRENT OPINION IN STRUCTURAL BIOLOGY,GB,CURRENT BIOLOGY LTD., LONDON, vol. 5, 1995, pages 224 - 228, XP000764926, ISSN: 0959-440X
GSCHWEND D A ET AL: "MOLECULAR DOCKING TOWARDS DRUG DISCOVERY", JOURNAL OF MOLECULAR RECOGNITION,GB,HEYDEN & SON LTD., LONDON, vol. 9, 1996, pages 175 - 186, XP000882526, ISSN: 0952-3499
BOEHM HANS-JOACHIM: "A novel computational tool for automated structure-based drug design.", JOURNAL OF MOLECULAR RECOGNITION, vol. 6, no. 3, 1993, pages 131 - 137, XP001008509, ISSN: 0952-3499
FRANCO M G ET AL: "STRUCTURAL BASIS FOR THE FUNCTION OF PYRIDOXINE 5'-PHOSPHATE SYNTHASE", STRUCTURE,CURRENT BIOLOGY LTD., PHILADELPHIA, PA,US, vol. 9, no. 3, March 2001 (2001-03-01), pages 245 - 253, XP001005211, ISSN: 0969-2126
DATABASE PROTEIN DATABANK [online] 28 March 2001 (2001-03-28), GARRIDO-FRANCO ET AL.: "crystal structure of pyridoxine 5'-phosphate synthase", XP002172864, retrieved from HTTP://WWW.RCSB.ORG/PDB/ Database accession no. 1hO1
DATABASE PROTEIN DATA BANK [online] 28 March 2001 (2001-03-28), GARRIDO-FRANCO ET AL.: "Crystal structure of pyridoxine synthase in complex with pyridoxine 5'-phosphate and inorganic phosphate.", XP002172865, retrieved from HTTP://WWW.RCSB.ORG/PDB/ Database accession no. 1hO4
EHRENSHAFT MARILYN ET AL: "A highly conserved sequence is a novel gene involved in de novo vitamin B6 biosynthesis.", PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES, vol. 96, no. 16, 3 August 1999 (1999-08-03), Aug. 3, 1999, pages 9374 - 9378, XP001008184, ISSN: 0027-8424
HILL R E ET AL: "BIOSYNTHESIS OF VITAMIN B-6", JOURNAL OF BIOLOGICAL CHEMISTRY, vol. 247, no. 6, 1972, pages 1869 - 1882, XP001008222, ISSN: 0021-9258
LABER BERND ET AL: "Vitamin B6 biosynthesis: Formation of pyridoxine 5'-phosphate from 4-(phosphohydroxy)-L-threonine and 1-deoxy-D-xylulose-5-phosphate by PdxA and PdxJ protein.", FEBS LETTERS, vol. 449, no. 1, 16 April 1999 (1999-04-16), pages 45 - 48, XP000999499, ISSN: 0014-5793
BAMBOROUGH P ET AL: "MODELING PROTEIN-LIGAND COMPLEXES", CURRENT OPINION IN STRUCTURAL BIOLOGY,CURRENT BIOLOGY LTD., LONDON,GB, vol. 6, no. 2, April 1996 (1996-04-01), pages 236 - 241, XP001005308, ISSN: 0959-440X
LYBRAND T P: "LIGAND-PROTEIN DOCKING AND RATIONAL DRUG DESIGN", CURRENT OPINION IN STRUCTURAL BIOLOGY,GB,CURRENT BIOLOGY LTD., LONDON, vol. 5, 1995, pages 224 - 228, XP000764926, ISSN: 0959-440X
GSCHWEND D A ET AL: "MOLECULAR DOCKING TOWARDS DRUG DISCOVERY", JOURNAL OF MOLECULAR RECOGNITION,GB,HEYDEN & SON LTD., LONDON, vol. 9, 1996, pages 175 - 186, XP000882526, ISSN: 0952-3499
BOEHM HANS-JOACHIM: "A novel computational tool for automated structure-based drug design.", JOURNAL OF MOLECULAR RECOGNITION, vol. 6, no. 3, 1993, pages 131 - 137, XP001008509, ISSN: 0952-3499
FRANCO M G ET AL: "STRUCTURAL BASIS FOR THE FUNCTION OF PYRIDOXINE 5'-PHOSPHATE SYNTHASE", STRUCTURE,CURRENT BIOLOGY LTD., PHILADELPHIA, PA,US, vol. 9, no. 3, March 2001 (2001-03-01), pages 245 - 253, XP001005211, ISSN: 0969-2126
DATABASE PROTEIN DATABANK [online] 28 March 2001 (2001-03-28), GARRIDO-FRANCO ET AL.: "crystal structure of pyridoxine 5'-phosphate synthase", XP002172864, retrieved from HTTP://WWW.RCSB.ORG/PDB/ Database accession no. 1hO1
DATABASE PROTEIN DATA BANK [online] 28 March 2001 (2001-03-28), GARRIDO-FRANCO ET AL.: "Crystal structure of pyridoxine synthase in complex with pyridoxine 5'-phosphate and inorganic phosphate.", XP002172865, retrieved from HTTP://WWW.RCSB.ORG/PDB/ Database accession no. 1hO4
EHRENSHAFT MARILYN ET AL: "A highly conserved sequence is a novel gene involved in de novo vitamin B6 biosynthesis.", PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES, vol. 96, no. 16, 3 August 1999 (1999-08-03), Aug. 3, 1999, pages 9374 - 9378, XP001008184, ISSN: 0027-8424
HILL R E ET AL: "BIOSYNTHESIS OF VITAMIN B-6", JOURNAL OF BIOLOGICAL CHEMISTRY, vol. 247, no. 6, 1972, pages 1869 - 1882, XP001008222, ISSN: 0021-9258
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