Title:
CRYSTALS STRUCTURE OF THE MOUSE APOPTOSIS-INDUCING FACTOR AIF AND APPLICATIONS THEREOF
Document Type and Number:
WIPO Patent Application WO2003089465
Kind Code:
A3
Abstract:
The invention relates to a polypeptide that modulates apoptosis or AIF redox activity comprising a variant or fragment of Apoptosis-Inducing Factor (AIF), a flavoprotein that can stimulate a caspase-independent cell-death pathway. This polypeptide may be at least identified, screened, designed or engineered used the data deposited in the Protein Data Bank under accession number 1GV4. Nucleic acids encoding polypeptides of the invention are also contemplated. Also disclosed are AIF variant proteins and methods for identifying, preparing or designing compounds that modulates AIF activities. Compounds identified by said methods are also contemplated. The invention also relates to computer-readable media and computerized methods for selecting or identifying AIF variants or compounds with AIF agonist or antagonist activity.
Inventors:
ALZARI PEDRO (FR)
Application Number:
PCT/IB2003/002102
Publication Date:
December 24, 2003
Filing Date:
April 22, 2003
Export Citation:
Assignee:
PASTEUR INSTITUT (FR)
CENTRE NAT RECH SCIENT (FR)
ALZARI PEDRO (FR)
CENTRE NAT RECH SCIENT (FR)
ALZARI PEDRO (FR)
International Classes:
C07K14/47; G01N33/50; (IPC1-7): C07K14/47; A61K38/17; C12N9/02; G01N33/68
Domestic Patent References:
| WO2000056752A2 | 2000-09-28 | |||
| WO2000020604A2 | 2000-04-13 | |||
| WO2000031254A2 | 2000-06-02 |
Other References:
LOEFFLER MARKUS ET AL: "Dominant cell death induction by extramitochondrially targeted apoptosis-inducing factor.", FASEB JOURNAL, vol. 15, no. 3, March 2001 (2001-03-01), pages 758 - 767, XP002256467, ISSN: 0892-6638
DAUGAS E. ET AL: "Apoptosis-inducing factor (AIF): a ubiquitous mitochondrial oxidoreductase involved in apoptosis", FEBS LETTERS, ELSEVIER SCIENCE PUBLISHERS, AMSTERDAM, NL, vol. 476, no. 3, 7 July 2000 (2000-07-07), pages 118 - 123, XP004337304, ISSN: 0014-5793
CANDE CELINE ET AL: "Apoptosis-inducing factor (AIF): A novel caspase-independent death effector released from mitochondria.", BIOCHIMIE (PARIS), vol. 84, no. 2-3, pages 215 - 222, XP002256468, ISSN: 0300-9084
NIENABER V L ET AL: "Discovering novel ligands for macromolecules using X-ray crystallographic screening", NATURE BIOTECHNOLOGY, NATURE PUBLISHING, US, vol. 18, no. 10, October 2000 (2000-10-01), pages 1105 - 1108, XP002250092, ISSN: 1087-0156
BLUNDELL T L: "Structure-based drug design", NATURE, MACMILLAN JOURNALS LTD. LONDON, GB, vol. 384, no. SUPPL, 7 November 1996 (1996-11-07), pages 23 - 26, XP002152956, ISSN: 0028-0836
SUSIN SANTOS A ET AL: "Molecular characterization of mitochondrial apoptosis-inducing factor", NATURE, MACMILLAN JOURNALS LTD. LONDON, GB, vol. 397, no. 6718, 4 February 1999 (1999-02-04), pages 441 - 446, XP002138394, ISSN: 0028-0836
JOZA NICHOLAS ET AL: "Essential role of the mitochondrial apoptosis-inducing factor in programmed cell death.", NATURE (LONDON), vol. 410, no. 6828, 2001, pages 549 - 554, XP002256469, ISSN: 0028-0836
MATE MARIA J ET AL: "The crystal structure of the mouse apoptosis-inducing factor AIF.", NATURE STRUCTURAL BIOLOGY, vol. 9, no. 6, 20 June 2002 (2002-06-20), pages 442 - 446, XP002256470, ISSN: 1072-8368
CANDE CELINE ET AL: "Apoptosis-inducing factor (AIF): Key to the conserved caspase-independent pathways of cell death?", JOURNAL OF CELL SCIENCE, vol. 115, no. 24, 15 December 2002 (2002-12-15), pages 4727 - 4734, XP002256471, ISSN: 0021-9533
DAUGAS E. ET AL: "Apoptosis-inducing factor (AIF): a ubiquitous mitochondrial oxidoreductase involved in apoptosis", FEBS LETTERS, ELSEVIER SCIENCE PUBLISHERS, AMSTERDAM, NL, vol. 476, no. 3, 7 July 2000 (2000-07-07), pages 118 - 123, XP004337304, ISSN: 0014-5793
CANDE CELINE ET AL: "Apoptosis-inducing factor (AIF): A novel caspase-independent death effector released from mitochondria.", BIOCHIMIE (PARIS), vol. 84, no. 2-3, pages 215 - 222, XP002256468, ISSN: 0300-9084
NIENABER V L ET AL: "Discovering novel ligands for macromolecules using X-ray crystallographic screening", NATURE BIOTECHNOLOGY, NATURE PUBLISHING, US, vol. 18, no. 10, October 2000 (2000-10-01), pages 1105 - 1108, XP002250092, ISSN: 1087-0156
BLUNDELL T L: "Structure-based drug design", NATURE, MACMILLAN JOURNALS LTD. LONDON, GB, vol. 384, no. SUPPL, 7 November 1996 (1996-11-07), pages 23 - 26, XP002152956, ISSN: 0028-0836
SUSIN SANTOS A ET AL: "Molecular characterization of mitochondrial apoptosis-inducing factor", NATURE, MACMILLAN JOURNALS LTD. LONDON, GB, vol. 397, no. 6718, 4 February 1999 (1999-02-04), pages 441 - 446, XP002138394, ISSN: 0028-0836
JOZA NICHOLAS ET AL: "Essential role of the mitochondrial apoptosis-inducing factor in programmed cell death.", NATURE (LONDON), vol. 410, no. 6828, 2001, pages 549 - 554, XP002256469, ISSN: 0028-0836
MATE MARIA J ET AL: "The crystal structure of the mouse apoptosis-inducing factor AIF.", NATURE STRUCTURAL BIOLOGY, vol. 9, no. 6, 20 June 2002 (2002-06-20), pages 442 - 446, XP002256470, ISSN: 1072-8368
CANDE CELINE ET AL: "Apoptosis-inducing factor (AIF): Key to the conserved caspase-independent pathways of cell death?", JOURNAL OF CELL SCIENCE, vol. 115, no. 24, 15 December 2002 (2002-12-15), pages 4727 - 4734, XP002256471, ISSN: 0021-9533
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