The three-dimensional structures of mutants of porphobilinogen deaminase: Toward an understanding of the structural basis of acute intermittent porphyria
Paul D. Brownlie
Laboratory of Molecular Biology, Department of Crystallography, Birkbeck College, University of London, Malet St., London WC1E7HX, United Kingdom
Search for more papers by this authorJon B. Cooper
Laboratory of Molecular Biology, Department of Crystallography, Birkbeck College, University of London, Malet St., London WC1E7HX, United Kingdom
Search for more papers by this authorSteve P. Wood
Laboratory of Molecular Biology, Department of Crystallography, Birkbeck College, University of London, Malet St., London WC1E7HX, United Kingdom
Search for more papers by this authorRichard Lambert
Laboratory of Molecular Biology, Department of Crystallography, Birkbeck College, University of London, Malet St., London WC1E7HX, United Kingdom
Search for more papers by this authorCorresponding Author
Tom L. Blundell
Laboratory of Molecular Biology, Department of Crystallography, Birkbeck College, University of London, Malet St., London WC1E7HX, United Kingdom
Laboratory of Molecular Biology, Department of Crystallography, Birkbeck College, University of London, Malet St., London WC1E7HX, UKSearch for more papers by this authorGordon V. Louie
Laboratory of Molecular Biology, Department of Crystallography, Birkbeck College, University of London, Malet St., London WC1E7HX, United Kingdom
Search for more papers by this authorPeter M. Jordan
School of Biological Sciences, Queen Mary and Westfield College, University of London, Mile End Road, London E14NS, United Kingdom
Search for more papers by this authorMartin J. Warren
School of Biological Sciences, Queen Mary and Westfield College, University of London, Mile End Road, London E14NS, United Kingdom
Search for more papers by this authorPaul D. Brownlie
Laboratory of Molecular Biology, Department of Crystallography, Birkbeck College, University of London, Malet St., London WC1E7HX, United Kingdom
Search for more papers by this authorJon B. Cooper
Laboratory of Molecular Biology, Department of Crystallography, Birkbeck College, University of London, Malet St., London WC1E7HX, United Kingdom
Search for more papers by this authorSteve P. Wood
Laboratory of Molecular Biology, Department of Crystallography, Birkbeck College, University of London, Malet St., London WC1E7HX, United Kingdom
Search for more papers by this authorRichard Lambert
Laboratory of Molecular Biology, Department of Crystallography, Birkbeck College, University of London, Malet St., London WC1E7HX, United Kingdom
Search for more papers by this authorCorresponding Author
Tom L. Blundell
Laboratory of Molecular Biology, Department of Crystallography, Birkbeck College, University of London, Malet St., London WC1E7HX, United Kingdom
Laboratory of Molecular Biology, Department of Crystallography, Birkbeck College, University of London, Malet St., London WC1E7HX, UKSearch for more papers by this authorGordon V. Louie
Laboratory of Molecular Biology, Department of Crystallography, Birkbeck College, University of London, Malet St., London WC1E7HX, United Kingdom
Search for more papers by this authorPeter M. Jordan
School of Biological Sciences, Queen Mary and Westfield College, University of London, Mile End Road, London E14NS, United Kingdom
Search for more papers by this authorMartin J. Warren
School of Biological Sciences, Queen Mary and Westfield College, University of London, Mile End Road, London E14NS, United Kingdom
Search for more papers by this authorAbstract
Mutations in the human gene for the enzyme porphobilinogen deaminase give rise to an inherited disease of heme biosynthesis, acute intermittent porphyria. Knowledge of the 3-dimensionai structure of human porphobilinogen deaminase, based on the structure of the bacterial enzyme, allows correlation of structure with gene organization and leads to an understanding of the relationship between mutations in the gene, structural and functional changes of the enzyme, and the symptoms of the disease. Most mutations occur in exons 10 and 12, often changing amino acids in the active site. Several of these are shown to be involved in binding the primer or substrate; none modifies Asp 84, which is essential for catalytic activity.
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