1fvo

CRYSTAL STRUCTURE OF HUMAN ORNITHINE TRANSCARBAMYLASE COMPLEXED WITH CARBAMOYL PHOSPHATE

spinqualitylabelsall models 1fvo, resolution 2.60Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 1fvo is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.6Å Ligands: CP Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease OTC_HUMAN Defects in OTC are the cause of ornithine carbamoyltransferase deficiency (OTCD) [MIM:311250. OTCD is an X-linked disorder of the urea cycle which causes a form of hyperammonemia. Mutations with no residual enzyme activity are always expressed in hemizygote males by a very severe neonatal hyperammonemic coma that generally proves to be fatal. Heterozygous females are either asymptomatic or express orotic aciduria spontaneously or after protein intake. The disorder is treatable with supplemental dietary arginine and low protein diet. The arbitrary classification of patients into the 'neonatal' group (clinical hyperammonemia in the first few days of life) and 'late' onset (clinical presentation after the neonatal period) has been used to differentiate severe from mild forms. [:] [:] Function OTC_HUMAN Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed 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 A (1 A=0.1 nm) 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 A 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. Human ornithine transcarbamylase: crystallographic insights into substrate recognition and conformational changes.,Shi D, Morizono H, Yu X, Tong L, Allewell NM, Tuchman M Biochem J. 2001 Mar 15;354(Pt 3):501-9. PMID:11237854 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Ornithine carbamoyltransferase 3D structures

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