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| 1 | The Study of Carbamoyl Phosphate Synthetase 1 Deficiency Sheds Light on the Mechanism for Switching On/Off the Urea Cycle显示文摘Carbamoyl phosphate synthetase 1(CPS1) deficiency(CPS1D) is an inborn error of the urea cycle having autosomal(2q34) recessive inheritance that can cause hyperammonemia and neonatal death or mental retardation. We analyzed the effects on CPS1 activity, kinetic parameters and enzyme stability of missense mutations reported in patients with CPS1 deficiency that map in the 20-k Da C-terminal domain of the enzyme. This domain turns on or off the enzyme depending on whether the essential allosteric activator of CPS1, N-acetylL-glutamate(NAG), is bound or is not bound to it. To carry out the present studies, we exploited a novel system that allows the expression in vitro and the purification of human CPS1, thus permitting site-directed mutagenesis. These studies have clarified disease causation by individual mutations, identifying functionally important residues, and revealing that a number of mutations decrease the affinity of the enzyme for NAG. Patients with NAG affinity-decreasing mutations might benefit from NAG site saturation therapy with N-carbamyl-Lglutamate(a registered drug, the analog of NAG). Our results, together with additional present and prior site-directed mutagenesis data for other residues mapping in this domain, suggest an NAG-triggered conformational change in the b4-a4 loop of the C-terminal domain of this enzyme. This change might be an early event in the NAG activation process. Molecular dynamics simulations that were restrained according to the observed effects of the mutations are consistent with this hypothesis, providing further backing for this structurally plausible signaling mechanism by which NAG could trigger urea cycle activation via CPS1. | Carmen Díez-Fernández José Gallego Johannes H?berle Javier Cervera Vicente Rubio | 2015 | Journal of Genetics and Genomics2015，42，5： | 7 |
| 2 | 显示文摘 | Klett J W Mcmillan A D Gallego N C | 2004 | Carbon2004，42，89： | 1 |
| 3 | 显示文摘 | Inman R D Gallegos K V Brause B D | 1984 | Am J Med1984，77，： | 1 |
| 4 | Repair of Damaged DNA by Arabidopsis Cell Extract显示文摘 | Li A Schuermann D Gallego F Kovalchuk I Tinland B | 2002 | Plant Cell2002，14，1： | 1 |
| 5 | The value of routine microbialin vestigation inventilator - associated pneumonia 显示文摘 | Rello J Gallego M Mariscai D | 1997 | Am JR espir Crit Care Med1997，156，： | 1 |
| 6 | Toughening of PA6/mEPDM Blends by Two Methods of Compounding, Extruder and Internal Mixer: Rheological, Morphological and Mechanical Characterization显示文摘 | R Gallego D Garc A-L Pez S L Pez-quintana | 2008 | Poly- mer Bulletin2008，60，： | 1 |
| 7 | Influence of the relative proportions of energy yielding nutrients on liver inter- mediary metabolism of the European eel 显示文摘 | Sucirez M D Hidalgo M C Gareia Gallego M | 1995 | Comparative Bio-chemistry and Physiology Part A: Physiology1995，111，3： | 1 |
| 8 | On the effectiveness of direct shipping strategy for the one warehouse multi-retailer Rsystems 显示文摘 | Gallego G Simchi-Levi D | 1990 | Management Science1990，36，： | 1 |
| 9 | Impact of fracture coating on fracture/matrix interactions in unsaturated porous medi显示文摘 | Thoma S G Gallegos D P Smith D M | 1992 | Water Resources Research1992，28，： | 1 |
| 10 | Fully automated quantitation of hepatitis B virus (HBV) DNA in human plasma by the COBAS AmpliPrep/COBAS TaqMan system显示文摘 | Hochberger S Althof D Gallegos de Schrott R | 2006 | J Clin Virol2006，35，4： | 1 |
| 11 | Pituitary stalk transection syndrome显示文摘 | Barbeau C Jouret B Gallegos D | 1998 | Arch Pediatr1998，5，3： | 1 |
| 12 | Seasonal mean pressure reconstruction for the North Atlantic (1750--1850) baaed on early marine data显示文摘 | Gallego D Garcia-Herrera R Ribera P | 2005 | Climate of the past2005，1，： | 1 |
| 13 | Purification and Characterization of an α -L -Rhamnosidase from AspergiUus terreus of Interest in Winemaking 显示文摘 | Gallego M V Pinaga F Ram6n D | 2001 | Journal of Food Science2001，66，2： | 1 |
| 14 | Start - up of thermophilic - dry anaerobic digestionof OFMSW using adapted modified SEBAC inoculum显示文摘 | Fdez - Guelfo L A Alvarez - Gallego C Maruqez D S | 2010 | Bioresource Technology2010，101，23： | 1 |
| 15 | A fast and efficient contact algorithm for fretting problems applied to fretting mode Ⅰ,Ⅱ and Ⅲ显示文摘 | Gallego L Nélias D Deyber S | | 0，，： | 1 |
| 16 | The value of routine mi- crobial investigation in ventilator-associated pneumonia显示文摘 | Rello J Gallego M Mariscal D | 1997 | Am J Respir Crit Care Med1997，156，1： | 1 |
| 17 | 显示文摘 | SANCHEZ D B E GALLEGO P J RECHE R A | 1993 | Arch Esp Urol1993，46，7： | 1 |
| 18 | The value of routine microbial investigation in ventilator-associated pneumonia显示文摘 | Gallego M Mariscal D | 1997 | Am J Respir Crit Care Med1997，156，： | 1 |
| 19 | Engineered in situ bioremediation of soil and groundwater polluted with weath- ered hydrocarbons显示文摘 | enendez-Vega D Gallego J L R Pelaez A I | 2007 | European Journal of Soil Biology2007，43，1： | 1 |
| 20 | Effects of heat treatment conditions on the thermal properties of mesophase pitch-derived graphitic foams显示文摘 | Klett J W McMillan A D Gallego N C | 2004 | Carbon2004，42，89： | 1 |
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