Literature DB >> 8544185

The molecular basis of ornithine transcarbamylase deficiency: modelling the human enzyme and the effects of mutations.

M Tuchman1, H Morizono, O Reish, X Yuan, N M Allewell.   

Abstract

Human ornithine transcarbamylase is a trimer with 46% amino acid sequence homology to the catalytic subunit of E coli aspartate transcarbamylase. Secondary structure predictions, distributions of hydrophilic and hydrophobic regions, and the pattern of conserved residues suggest that the three dimensional structures of the two proteins are likely to be similar. A three dimensional model of ornithine transcarbamylase was generated from the crystal structure of the catalytic subunit of E coli aspartate transcarbamylase in the holoenzyme, by aligning the sequences, building in gaps, and minimising the energy. The binding sites for carbamyl phosphate in both enzymes are similar and the ornithine binding site in ornithine transcarbamylase appears to be in the same location as the L-aspartate binding site in aspartate transcarbamylase, with negatively charged side chains replaced by positively charged residues. Mutations in the ornithine transcarbamylase gene found in patients with hyperammonaemia of the "neonatal type" are clustered in important structural or functional domains, either in the interior of the protein, at the active site, or at the interchain interface, while mutations found in patients with milder "late onset" disease are located primarily on the surface of the protein. The predicted effects of all known missense mutations and in frame deletions in the ornithine transcarbamylase gene on the structure and function of the mature enzyme are described.

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Year:  1995        PMID: 8544185      PMCID: PMC1051666          DOI: 10.1136/jmg.32.9.680

Source DB:  PubMed          Journal:  J Med Genet        ISSN: 0022-2593            Impact factor:   6.318


  27 in total

1.  Ornithine carbamoyltransferase from Escherichia coli W. Purification, structure and steady-state kinetic analysis.

Authors:  C Legrain; V Stalon
Journal:  Eur J Biochem       Date:  1976-03-16

2.  Isolation and characterization of ornithine transcarbamylase from normal human liver.

Authors:  F Kalousek; B François; L E Rosenberg
Journal:  J Biol Chem       Date:  1978-06-10       Impact factor: 5.157

3.  Chemical and biological evolution of nucleotide-binding protein.

Authors:  M G Rossmann; D Moras; K W Olsen
Journal:  Nature       Date:  1974-07-19       Impact factor: 49.962

4.  Allosteric interactions in aspartate transcarbamylase. II. Evidence for different conformational states of the protein in the presence and absence of specific ligands.

Authors:  J C Gerhart; H K Schachman
Journal:  Biochemistry       Date:  1968-02       Impact factor: 3.162

5.  Protein differentiation: a comparison of aspartate transcarbamoylase and ornithine transcarbamoylase from Escherichia coli K-12.

Authors:  J E Houghton; D A Bencini; G A O'Donovan; J R Wild
Journal:  Proc Natl Acad Sci U S A       Date:  1984-08       Impact factor: 11.205

6.  Zn(II)-induced cooperativity of Escherichia coli ornithine transcarbamoylase.

Authors:  L C Kuo; W N Lipscomb; E R Kantrowitz
Journal:  Proc Natl Acad Sci U S A       Date:  1982-04       Impact factor: 11.205

7.  Structure and expression of a complementary DNA for the nuclear coded precursor of human mitochondrial ornithine transcarbamylase.

Authors:  A L Horwich; W A Fenton; K R Williams; F Kalousek; J P Kraus; R F Doolittle; W Konigsberg; L E Rosenberg
Journal:  Science       Date:  1984-06-08       Impact factor: 47.728

8.  Kinetic analysis of a new human ornithine carbamoyltransferase variant.

Authors:  L Cathelineau; P Briand; F Petit; J P Nuyts; J P Farriaux; P P Kamoun
Journal:  Biochim Biophys Acta       Date:  1980-07-10

9.  Human ornithine transcarbamylase locus mapped to band Xp21.1 near the Duchenne muscular dystrophy locus.

Authors:  V Lindgren; B de Martinville; A L Horwich; L E Rosenberg; U Francke
Journal:  Science       Date:  1984-11-09       Impact factor: 47.728

Review 10.  Mutations and polymorphisms in the human ornithine transcarbamylase gene: mutation update addendum.

Authors:  M Tuchman; R J Plante
Journal:  Hum Mutat       Date:  1995       Impact factor: 4.878

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  16 in total

Review 1.  Ornithine carbamoyltransferase deficiency.

Authors:  J E Wraith
Journal:  Arch Dis Child       Date:  2001-01       Impact factor: 3.791

2.  Prenatal molecular diagnosis of severe ornithine carbamoyltransferase deficiency due to a novel mutation, E181G.

Authors:  A K Topaloglu; C Sansaricq; J E Fox; A E Bale; M Tuchman; R J Desnick
Journal:  J Inherit Metab Dis       Date:  1999-02       Impact factor: 4.982

3.  Substrate-induced conformational change in a trimeric ornithine transcarbamoylase.

Authors:  Y Ha; M T McCann; M Tuchman; N M Allewell
Journal:  Proc Natl Acad Sci U S A       Date:  1997-09-02       Impact factor: 11.205

4.  Overexpression, purification, crystallization and preliminary structural studies of catabolic ornithine transcarbamylase from Lactobacillus hilgardii.

Authors:  Blanca de Las Rivas; Héctor Rodríguez; Iván Angulo; Rosario Muñoz; José M Mancheño
Journal:  Acta Crystallogr Sect F Struct Biol Cryst Commun       Date:  2007-06-11

5.  Identification of 'private' mutations in patients with ornithine transcarbamylase deficiency.

Authors:  M Tuchman; H Morizono; B S Rajagopal; R J Plante; N M Allewell
Journal:  J Inherit Metab Dis       Date:  1997-08       Impact factor: 4.982

6.  Expression, purification and kinetic characterization of wild-type human ornithine transcarbamylase and a recurrent mutant that produces 'late onset' hyperammonaemia.

Authors:  H Morizono; M Tuchman; B S Rajagopal; M T McCann; C D Listrom; X Yuan; D Venugopal; G Barany; N M Allewell
Journal:  Biochem J       Date:  1997-03-01       Impact factor: 3.857

7.  Mutation detection in 65 families with a possible diagnosis of ornithine carbamoyltransferase deficiency including 14 novel mutations.

Authors:  S Genet; T Cranston; H R Middleton-Price
Journal:  J Inherit Metab Dis       Date:  2000-11       Impact factor: 4.982

8.  Acetylornithine transcarbamylase: a novel enzyme in arginine biosynthesis.

Authors:  Hiroki Morizono; Juan Cabrera-Luque; Dashuang Shi; Rene Gallegos; Saori Yamaguchi; Xiaolin Yu; Norma M Allewell; Michael H Malamy; Mendel Tuchman
Journal:  J Bacteriol       Date:  2006-04       Impact factor: 3.490

9.  The biochemical and molecular spectrum of ornithine transcarbamylase deficiency.

Authors:  M Tuchman; H Morizono; B S Rajagopal; R J Plante; N M Allewell
Journal:  J Inherit Metab Dis       Date:  1998       Impact factor: 4.982

Review 10.  Mammalian N-acetylglutamate synthase.

Authors:  Hiroki Morizono; Ljubica Caldovic; Dashuang Shi; Mendel Tuchman
Journal:  Mol Genet Metab       Date:  2004-04       Impact factor: 4.797

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