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Robert Edgar (2004)
MUSCLE: multiple sequence alignment with high accuracy and high throughput.Nucleic acids research, 32 5
Y. Chien, W. Hwu (2009)
Novel human pathological mutations. Gene symbol: GLA. Disease: Fabry disease.Human genetics, 125 3
E. Alonso, J. Cervera, Antonio Garcia-España, E. Bendala, Vicente Rubio (1992)
Oxidative inactivation of carbamoyl phosphate synthetase (ammonia). Mechanism and sites of oxidation, degradation of the oxidized enzyme, and inactivation by glycerol, EDTA, and thiol protecting agents.The Journal of biological chemistry, 267 7
M. Tuchman, Brendan Lee, U. Lichter-Konecki, M. Summar, M. Yudkoff, S. Cederbaum, D. Kerr, G. Diaz, M. Seashore, Hye-Seung Lee, R. McCarter, J. Krischer, M. Batshaw (2008)
Cross-sectional multicenter study of patients with urea cycle disorders in the United States.Molecular genetics and metabolism, 94 4
A. Eeds, L. Hall, M. Yadav, A. Willis, S. Summar, A. Putnam, F. Barr, M. Summar (2006)
The frequent observation of evidence for nonsense-mediated decay in RNA from patients with carbamyl phosphate synthetase I deficiency.Molecular genetics and metabolism, 89 1-2
M. Summar, L. Hall, B. Christman, F. Barr, Heidi Smith, A. Kallianpur, N. Brown, M. Yadav, A. Willis, A. Eeds, Emma Cermak, S. Summar, Ann Wilson, M. Arvin, A. Putnam, M. Wills, G. Cunningham (2004)
Environmentally determined genetic expression: clinical correlates with molecular variants of carbamyl phosphate synthetase I.Molecular genetics and metabolism, 81 Suppl 1
E. Hart, S. Powers-Lee (2009)
Role of Cys-1327 and Cys-1337 in Redox Sensitivity and Allosteric Monitoring in Human Carbamoyl Phosphate Synthetase*Journal of Biological Chemistry, 284
O. Lichtarge, K. Yamamoto, F. Cohen (1997)
Identification of functional surfaces of the zinc binding domains of intracellular receptors.Journal of molecular biology, 274 3
T. Aoshima, M. Kajita, Y. Sekido, Satoshi Kikuchi, I. Yasuda, T. Saheki, Kazuyoshi Watanabe, K. Shimokata, T. Niwa (2001)
Novel Mutations (H337R and 238–362del) in the CPS1 Gene Cause Carbamoyl Phosphate Synthetase I DeficiencyHuman Heredity, 52
M. Summar (1998)
Molecular genetic research into carbamoyl-phosphate synthase I: Molecular defects and linkage markersJournal of Inherited Metabolic Disease, 21
R. Laskowski, E. Hutchinson, A. Michie, A. Wallace, Martin Jones, J. Thornton, J. Thornton (1997)
PDBsum: a Web-based database of summaries and analyses of all PDB structures.Trends in biochemical sciences, 22 12
G. Shambaugh (1977)
Urea biosynthesis I. The urea cycle and relationships to the citric acid cycle.The American journal of clinical nutrition, 30 12
V. Rubio (1993)
Structure-function studies in carbamoyl phosphate synthetases.Biochemical Society transactions, 21 1
Khayat (2009)
336Hum Genet, 125
K. Arnold, L. Bordoli, J. Kopp, T. Schwede (2006)
The SWISS-MODEL workspace: a web-based environment for protein structure homology modellingBioinformatics, 22 2
A. Horwich, F. Kalousek, W. Fenton, R. Pollock, L. Rosenberg (1986)
Targeting of pre-ornithine transcarbamylase to mitochondria: Definition of critical regions and residues in the leader peptideCell, 44
I. Mihalek, I. Res, O. Lichtarge (2006)
Evolutionary trace report_maker: a new type of service for comparative analysis of proteinsBioinformatics, 22 13
Hui Yao, D. Kristensen, I. Mihalek, M. Sowa, C. Shaw, M. Kimmel, L. Kavraki, O. Lichtarge (2003)
An accurate, sensitive, and scalable method to identify functional sites in protein structures.Journal of molecular biology, 326 1
H. Krebs, K. Henseleit (2005)
Untersuchungen über die Harnstoffbildung im TierkörperKlinische Wochenschrift, 11
V. Fresquet, P. Mora, L. Rochera, S. Ramón-Maiques, V. Rubio, J. Cervera (2000)
Site-directed mutagenesis of the regulatory domain of Escherichia coli carbamoyl phosphate synthetase identifies crucial residues for allosteric regulation and for transduction of the regulatory signals.Journal of molecular biology, 299 4
H. Windmueller, A. Spaeth (1981)
Source and fate of circulating citrulline.The American journal of physiology, 241 6
Hiroaki Ono, T. Suto, Y. Kinoshita, T. Sakano, Takeki Furue, T. Ohta (2009)
A case of carbamoyl phosphate synthetase 1 deficiency presenting symptoms at one month of ageBrain and Development, 31
S. Powers-Lee, K. Corina (1986)
Domain structure of rat liver carbamoyl phosphate synthetase I.The Journal of biological chemistry, 261 33
S. Mitchell, C. Ellingson, Thomas Coyne, L. Hall, M. Neill, Natalie Christian, C. Higham, S. Dobrowolski, M. Tuchman, M. Summar (2009)
Genetic variation in the urea cycle: a model resource for investigating key candidate genes for common diseasesHuman Mutation, 30
V. Klaus, T. Vermeulen, B. Minassian, N. Israelian, K. Engel, Allan Lund, K. Roebrock, Ernst Christensen, Johannes Häberle (2009)
Highly variable clinical phenotype of carbamylphosphate synthetase 1 deficiency in one family: an effect of allelic variation in gene expression?Clinical Genetics, 76
R. Hoshide (1998)
[Carbamyl phosphate synthetase I deficiency].Ryoikibetsu shokogun shirizu, 18 Pt 1
J. Cervera, F. Conejero-Lara, J. Ruiz-Sanz, M. Galisteo, P. Mateo, C. Lusty, V. Rubio (1993)
The influence of effectors and subunit interactions on Escherichia coli carbamoyl-phosphate synthetase studied by differential scanning calorimetry.The Journal of biological chemistry, 268 17
W. Kabsch, C. Sander (1983)
Dictionary of protein secondary structure: Pattern recognition of hydrogen‐bonded and geometrical featuresBiopolymers, 22
A. Meister (1989)
Mechanism and regulation of the glutamine-dependent carbamyl phosphate synthetase of Escherichia coli.Advances in enzymology and related areas of molecular biology, 62
V. Rubio, S. Grisolía (1981)
Human carbamoylphosphate synthetase I.Enzyme, 26 5
A. Eeds, D. Mortlock, R. Wade-Martins, M. Summar (2007)
Assessing the functional characteristics of synonymous and nonsynonymous mutation candidates by use of large DNA constructs.American journal of human genetics, 80 4
H. Nyunoya, Karen Brogfie, E. Widgren, J. Lusty (1985)
Characterization and derivation of the gene coding for mitochondrial carbamyl phosphate synthetase I of rat.The Journal of biological chemistry, 260 16
Albert Ribes-Zamora, I. Mihalek, O. Lichtarge, A. Bertuch (2007)
Distinct faces of the Ku heterodimer mediate DNA repair and telomeric functionsNature Structural &Molecular Biology, 14
O. Lichtarge, H. Bourne, F. Cohen (1996)
An evolutionary trace method defines binding surfaces common to protein families.Journal of molecular biology, 257 2
F. Javid-Majd, M. Stapleton, M. Harmon, B. Hanks, L. Mullins, F. Raushel (1996)
Comparison of the functional differences for the homologous residues within the carboxy phosphate and carbamate domains of carbamoyl phosphate synthetase.Biochemistry, 35 45
S. Funghini, M. Donati, E. Pasquini, E. Zammarchi, A. Morrone (2003)
Structural organization of the human carbamyl phosphate synthetase I gene (CPS1) and identification of two novel genetic lesionsHuman Mutation, 22
U. Finckh, A. Kohlschütter, H. Schäfer, K. Sperhake, J. Colombo, A. Gal (1998)
Prenatal diagnosis of carbamoyl phosphate synthetase I deficiency by identification of a missense mutation in CPS1Human Mutation, 12
Y. Wakutani, H. Nakayasu, T. Takeshima, N. Mori, K. Kobayashi, F. Endo, K. Nakashima (2001)
[A case of late-onset carbamoyl phosphate synthetase I deficiency, presenting periodic psychotic episodes coinciding with menstrual periods].Rinsho shinkeigaku = Clinical neurology, 41 11
Faiza Baameur, Daniel Morgan, Hui Yao, T. Tran, Richard Hammitt, S. Sabui, J. McMurray, O. Lichtarge, R. Clark (2010)
Role for the Regulator of G-Protein Signaling Homology Domain of G Protein-Coupled Receptor Kinases 5 and 6 in β2-Adrenergic Receptor and Rhodopsin PhosphorylationMolecular Pharmacology, 77
M. Loscalzo, R. Galczynski, A. Hamosh, M. Summar, J. Chinsky, G. Thomas (2004)
Interstitial deletion of chromosome 2q32‐34 associated with multiple congenital anomalies and a urea cycle defect (CPS I deficiency)American Journal of Medical Genetics Part A, 128A
V. Rubio, G. Ramponi, S. Grisolía (1981)
Carbamoyl phosphate synthetase I of human liver. Purification, some properties and immunological cross-reactivity with the rat liver enzyme.Biochimica et biophysica acta, 659 1
I. Mihalek, I. Res, Hui Yao, O. Lichtarge (2003)
Combining inference from evolution and geometric probability in protein structure evaluation.Journal of molecular biology, 331 1
K. Oyanagi, Kimie Nakamura, H. Sogawa, H. Tsukazaki, R. Minami, T. Nakao (1980)
A Study of Urea-synthesizing Enzymes in Prenatal and Postnatal Human LiverPediatric Research, 14
Amna Saeed-Kothe, S. Powers-Lee (2003)
Gain of Glutaminase Function in Mutants of the Ammonia-specific Frog Carbamoyl Phosphate Synthetase*Journal of Biological Chemistry, 278
Alonso (1995)
377Eur J Biochem, 229
T. Falik-Zaccai, Nechama Kfir, Pnina Frenkel, C. Cohen, M. Tanus, H. Mandel, S. Shihab, S. Morkos, Salameh Aaref, M. Summar, M. Khayat (2008)
Population screening in a Druze community: the challenge and the rewardGenetics in Medicine, 10
Daniel Morgan, David Kristensen, David Mittelman, O. Lichtarge (2006)
ET viewer: an application for predicting and visualizing functional sites in protein structuresBioinformatics, 22 16
M. Summar, D. Dobbelaere, S. Brusilow, Brendan Lee (2008)
Diagnosis, symptoms, frequency and mortality of 260 patients with urea cycle disorders from a 21‐year, multicentre study of acute hyperammonaemic episodesActa Pædiatrica, 97
Krebs (1932)
325Hoppe-Seyler's Zeitschrift für Physiologische Chemie, 210
I. Mihalek, I. Res, O. Lichtarge (2004)
A family of evolution-entropy hybrid methods for ranking protein residues by importance.Journal of molecular biology, 336 5
J. Schofield (1993)
Molecular studies on an ancient gene encoding for carbamoyl-phosphate synthetase.Clinical science, 84 2
E. Alonso, E. Alonso, V. Rubio (1995)
Affinity cleavage of carbamoyl-phosphate synthetase I localizes regions of the enzyme interacting with the molecule of ATP that phosphorylates carbamate.European journal of biochemistry, 229 2
C. Chothia, A. Lesk (1986)
The relation between the divergence of sequence and structure in proteins.The EMBO Journal, 5
S. Pekkala, A. Martinez, B. Barcelona, I. Yefimenko, U. Finckh, V. Rubio, J. Cervera (2010)
Understanding carbamoyl‐phosphate synthetase I (CPS1) deficiency by using expression studies and structure‐based analysisHuman Mutation, 31
(2008)
Novel human pathological mutationsHuman Genetics, 123
Wakutani (2001)
780Rinsho Shinkeigaku, 41
Haraguchi Yougo, Uchino Takako, Takiguchi Masaki, F. Endo, Mori Masataka, I. Matsuda (1991)
Cloning and sequence of a cDNA encoding human carbamyl phosphate synthetase I: molecular analysis of hyperammonemia.Gene, 107 2
R. Hoshide, T. Matsuura, Y. Haraguchi, F. Endo, M. Yoshinaga, I. Matsuda (1993)
Carbamyl phosphate synthetase I deficiency. One base substitution in an exon of the CPS I gene causes a 9-basepair deletion due to aberrant splicing.The Journal of clinical investigation, 91 5
T. Aoshima, M. Kajita, Y. Sekido, S. Mimura, A. Itakura, I. Yasuda, T. Saheki, Kazuyoshi Watanabe, K. Shimokata, T. Niwa (2001)
Carbamoyl phosphate synthetase I deficiency: molecular genetic findings and prenatal diagnosisPrenatal Diagnosis, 21
Meister (1989)
315Adv Enzymol Relat Areas Mol Biol, 62
L. Wong, W. Craigen, W. O'Brien (1994)
Postpartum Coma and Death due to Carbamoyl-Phosphate Synthetase I DeficiencyAnnals of Internal Medicine, 120
Jeremiah Ryall, Mai Nguyen, Moise Bendayan, Gordon Shore (1985)
Expression of nuclear genes encoding the urea cycle enzymes, carbamoyl-phosphate synthetase I and ornithine carbamoyl transferase, in rat liver and intestinal mucosa.European journal of biochemistry, 152 2
M. Summar, L. Hall, A. Eeds, H. Hutcheson, A. Kuo, A. Willis, V. Rubio, M. Arvin, J. Schofield, E. Dawson (2003)
Characterization of genomic structure and polymorphisms in the human carbamyl phosphate synthetase I gene.Gene, 311
K Ihara, H Nakayama, S Hikino, T. Hara (1999)
Mutation in CPS1Hum Genet, 105
Windmueller (1981)
E473Am J Physiol, 241
M. Neill, J. Aschner, F. Barr, M. Summar (2009)
Quantitative RT-PCR comparison of the urea and nitric oxide cycle gene transcripts in adult human tissues.Molecular genetics and metabolism, 97 2
Johannes Häberle, Eva Schmidt, Silke Pauli, B. Rapp, E. Christensen, Benedicht Wermuth, H. Koch (2003)
Gene structure of human carbamylphosphate synthetase 1 and novel mutations in patients with neonatal onsetHuman Mutation, 21
Zhen Wang, J. Moult (2001)
SNPs, protein structure, and diseaseHuman Mutation, 17
M. Khayat (2009)
Novel human pathological mutations. Gene symbol: CPS1. Disease: carbamoyl phosphate synthetase I deficiency.Human genetics, 125 3
Vibha Ahuja, S. Powers-Lee (2008)
Human carbamoyl-phosphate synthetase: Insight into N-acetylglutamate interaction and the functional effects of a common single nucleotide polymorphismJournal of Inherited Metabolic Disease, 31
J. Thoden, G. Wesenberg, F. Raushel, H. Holden (1999)
Carbamoyl phosphate synthetase: closure of the B-domain as a result of nucleotide binding.Biochemistry, 38 8
Ihara (1999)
375Hum Genet, 105
S. Pekkala, A. Martinez, B. Barcelona, J. Gallego, E. Bendala, I. Yefimenko, V. Rubio, J. Cervera (2009)
Structural insight on the control of urea synthesis: identification of the binding site for N-acetyl-L-glutamate, the essential allosteric activator of mitochondrial carbamoyl phosphate synthetase.The Biochemical journal, 424 2
K. Kurokawa, T. Yorifuji, M. Kawai, T. Momoi, H. Nagasaka, M. Takayanagi, Keiko Kobayashi, M. Yoshino, T. Kosho, M. Adachi, H. Otsuka, Shigenori Yamamoto, T. Murata, A. Suenaga, T. Ishii, K. Terada, N. Shimura, K. Kiwaki, H. Shintaku, M. Yamakawa, H. Nakabayashi, Y. Wakutani, T. Nakahata (2007)
Molecular and clinical analyses of Japanese patients with carbamoylphosphate synthetase 1 (CPS1) deficiencyJournal of Human Genetics, 52
I. Yefimenko, V. Fresquet, C. Marco-Marín, V. Rubio, J. Cervera (2005)
Understanding carbamoyl phosphate synthetase deficiency: impact of clinical mutations on enzyme functionality.Journal of molecular biology, 349 1
M. Stapleton, F. Javid-Majd, M. Harmon, B. Hanks, J. Grahmann, L. Mullins, F. Raushel (1996)
Role of conserved residues within the carboxy phosphate domain of carbamoyl phosphate synthetase.Biochemistry, 35 45
T. Uchino, F. Endo, I. Matsuda (1998)
Neurodevelopmental outcome of long-term therapy of urea cycle disorders in JapanJournal of Inherited Metabolic Disease, 21
L. Rodríguez-Aparicio, A. Guadalajara, V. Rubio (1989)
Physical location of the site for N-acetyl-L-glutamate, the allosteric activator of carbamoyl phosphate synthetase, in the 20-kilodalton COOH-terminal domain.Biochemistry, 28 7
B. Rapp, J. Häberle, M. Linnebank, B. Wermuth, T. Marquardt, E. Harms, H. Koch (2001)
Genetic analysis of carbamoylphosphate synthetase I and ornithine transcarbamylase deficiency using fibroblastsEuropean Journal of Pediatrics, 160
V. Rubio, J. Cervera (1995)
The carbamoyl-phosphate synthase family and carbamate kinase: structure-function studies.Biochemical Society transactions, 23 4
J. Thoden, H. Holden, G. Wesenberg, F. Raushel, I. Rayment (1997)
Structure of carbamoyl phosphate synthetase: a journey of 96 A from substrate to product.Biochemistry, 36 21
O. Pierrat, F. Raushel (2002)
A functional analysis of the allosteric nucleotide monophosphate binding site of carbamoyl phosphate synthetase.Archives of biochemistry and biophysics, 400 1
Deficiency of carbamoyl phosphate synthetase I (CPSI) results in hyperammonemia ranging from neonatally lethal to environmentally induced adult‐onset disease. Over 24 years, analysis of tissue and DNA samples from 205 unrelated individuals diagnosed with CPSI deficiency (CPSID) detected 192 unique CPS1 gene changes, of which 130 are reported here for the first time. Pooled with the already reported mutations, they constitute a total of 222 changes, including 136 missense, 15 nonsense, 50 changes of other types resulting in enzyme truncation, and 21 other changes causing in‐frame alterations. Only ∼10% of the mutations recur in unrelated families, predominantly affecting CpG dinucleotides, further complicating the diagnosis because of the “private” nature of such mutations. Missense changes are unevenly distributed along the gene, highlighting the existence of CPSI regions having greater functional importance than other regions. We exploit the crystal structure of the CPSI allosteric domain to rationalize the effects of mutations affecting it. Comparative modeling is used to create a structural model for the remainder of the enzyme. Missense changes are found to directly correlate, respectively, with the one‐residue evolutionary importance and inversely correlate with solvent accessibility of the mutated residue. This is the first large‐scale report of CPS1 mutations spanning a wide variety of molecular defects highlighting important regions in this protein. Hum Mutat 32:1–11, 2011. © 2011 Wiley‐Liss, Inc.
Human Mutation – Wiley
Published: Jun 1, 2011
Keywords: urea cycle; CPS1; hyperammonemia; structure; evolutionary
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