scholarly journals Carbamoyl Phosphate Synthetase, Ornithine Transcarbamylase, and Aspartate Transcarbamylase Activities in the Pea Ovary

1989 ◽  
Vol 90 (4) ◽  
pp. 1565-1569 ◽  
Author(s):  
Antonio Garcia-España ◽  
Juan Carbonell ◽  
Vicente Rubio
Keyword(s):  
Ornithine Transcarbamylase ◽  
Carbamoyl Phosphate Synthetase ◽  
Carbamoyl Phosphate ◽  
Aspartate Transcarbamylase

scholarly journals carbamoyl-phosphate synthetase 2,aspartate transcarbamylase, anddihydroorotase(cad) regulates Notch signaling and vascular development in zebrafish

2014 ◽  
Vol 244 (1) ◽  
pp. 1-9 ◽  
Author(s):  
Baptiste Coxam ◽  
Christine Neyt ◽  
Daniela R. Grassini ◽  
Ludovic Le Guen ◽  
Kelly A. Smith ◽  
...  
Keyword(s):  
Notch Signaling ◽  
Vascular Development ◽  
Carbamoyl Phosphate Synthetase ◽  
Carbamoyl Phosphate ◽  
Aspartate Transcarbamylase

scholarly journals Substitutions in hamster CAD carbamoyl-phosphate synthetase alter allosteric response to 5-phosphoribosyl-alpha-pyrophosphate (PRPP) and UTP

2004 ◽  
Vol 378 (3) ◽  
pp. 991-998 ◽  
Author(s):  
Christine Q. SIMMONS ◽  
Alan J. SIMMONS ◽  
Aaron HAUBNER ◽  
Amber REAM ◽  
Jeffrey N. DAVIDSON
Keyword(s):  
De Novo ◽  
Binding Pocket ◽  
Tryptophan Residue ◽  
Carbamoyl Phosphate Synthetase ◽  
Carbamoyl Phosphate ◽  
Aspartate Transcarbamylase ◽  
Inosine Monophosphate ◽  
E Coli ◽  
Mammalian Enzyme ◽  
Cad Protein

CPSase (carbamoyl-phosphate synthetase II), a component of CAD protein (multienzymic protein with CPSase, aspartate transcarbamylase and dihydro-orotase activities), catalyses the regulated steps in the de novo synthesis of pyrimidines. Unlike the orthologous Escherichia coli enzyme that is regulated by UMP, inosine monophosphate and ornithine, the mammalian CPSase is allosterically inhibited by UTP, and activated by PRPP (5-phosphoribosyl-α-pyrophosphate) and phosphorylation. Four residues (Thr974, Lys993, Lys954 and Thr977) are critical to the E. coli inosine monophosphate/UMP-binding pocket. In the present study, three of the corresponding residues in the hamster CPSase were altered to determine if they affect either PRPP activation or UTP inhibition. Substitution of the hamster residue, positionally equivalent to Thr974 in the E. coli enzyme, with alanine residue led to an enzyme with 5-fold lower activity and a near loss of PRPP activation. Whereas replacement of the tryptophan residue at position 993 had no effect, an Asp992→Asn substitution yielded a much-activated enzyme that behaved as if PRPP was present. The substitution Lys954→Glu had no effect on PRPP stimulation. Only modest decreases in UTP inhibitions were observed with each of the altered CPSases. The results also show that while PRPP and UTP can act simultaneously, PRPP activation is dominant. Apparently, UTP and PRPP have distinctly different associations within the mammalian enzyme. The findings of the present study may prove relevant to the neuropathology of Lesch–Nyhan syndrome.

Human ornithine transcarbamylase: crystallographic insights into substrate recognition and conformational changes

2001 ◽  
Vol 354 (3) ◽  
pp. 501-509 ◽  
Author(s):  
Dashuang SHI ◽  
Hiroki MORIZONO ◽  
Xiaolin YU ◽  
Liang TONG ◽  
Norma M. ALLEWELL ◽  
...  
Keyword(s):  
Conformational Changes ◽  
Substrate Recognition ◽  
Data Bank ◽  
Structural Features ◽  
Ornithine Transcarbamylase ◽  
Structural Factors ◽  
Carbamoyl Phosphate ◽  
Aspartate Transcarbamylase ◽  
R Factor ◽  
Rutgers University

Two crystal structures of human ornithine transcarbamylase (OTCase) complexed with the substrate carbamoyl phosphate (CP) have been solved. One structure, whose crystals were prepared by substituting N-phosphonacetyl-L-ornithine (PALO) liganded crystals with CP, has been refined at 2.4 Å (1 Å = 0.1nm) resolution to a crystallographic R factor of 18.4%. The second structure, whose crystals were prepared by co-crystallization with CP, has been refined at 2.6 Å resolution to a crystallographic R factor of 20.2%. These structures provide important new insights into substrate recognition and ligand-induced conformational changes. Comparison of these structures with the structures of OTCase complexed with the bisubstrate analogue PALO or CP and L-norvaline reveals that binding of the first substrate, CP, induces a global conformational change involving relative domain movement, whereas the binding of the second substrate brings the flexible SMG loop, which is equivalent to the 240s loop in aspartate transcarbamylase, into the active site. The model reveals structural features that define the substrate specificity of the enzyme and that regulate the order of binding and release of products. Atomic coordinates and structural factors (codes 1EP9 and 1FVO respectively) have been deposited in the Protein Data Bank, Research Collaboratory for Structural Bioinformatics, Rutgers University, New Brunswick, NJ, U.S.A.

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