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Catalytic Site Atlas

CSA LITERATURE entry for 1akm

E.C. nameornithine carbamoyltransferase
SpeciesEscherichia coli (Bacteria)
E.C. Number (IntEnz) 2.1.3.3
CSA Homologues of 1akmThere are 18 Homologs
CSA Entries With UniProtID P04391
CSA Entries With EC Number 2.1.3.3
PDBe Entry 1akm
PDBSum Entry 1akm
MACiE Entry 1akm

Literature Report

IntroductionDeleterious mutations in the ornithine carbamoyltransferase gene in humans cause clinical hyperammonemia, causing neurological symptoms and eventually death. Establishing the structural basis of such mutations is therefore of clinical importance.
MechansimCys 273 forms a proton relay system with Asp 231 and the alpha amino group of the ornithine. A tetrahedral intermediate is stabilised by Gln 136, which can form a hydrogen bond to the positive N-delta of ornithine, and by Arg 106, Arg 319 and His 133, which can form hydrogen bonds to the oxyanion that results from nucleophilic attack on the carbonyl. The proton attached to Cys 273 may leave the active site via a chain of ordered water molecules.
Reference pubmed ID 9253409 pointed out a similarity between the triad of residues His272, Cys273 and Glu299 are similar to those of the catalytic triads of thiol peptidases. However, use of the template-matching program TESS and the structural alignment program ProFit showed that the RMSD of these fits was very tenuous and the similarity is likely to be coincidental. Reference pubmed ID 9852088 does not believe the catalytic triad is significant.
Reaction

Catalytic Sites for 1akm

Annotated By Reference To The Literature - Site 1 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
GlnA136137macie:sideChainStabilises accumulation of positive charge on the N-delta of L-ornithine as this atom attacks the carbonyl of carbamoyl phosphate.
CysA273274macie:sideChainDeprotonates the delta-amino group of L-ornithine to allow it to attack carbamoyl phosphate.
AspA231232macie:sideChainStabilises the thiolate from of the sulfhydryl group of Cys 273, enabling it to accept a proton from L-ornithine.
ArgA106107macie:sideChainStabilises accumulation of negative charge on the carbonyl oxygen of carbamoyl phosphate during nucleophilic attack by L-ornithine.
HisA133134macie:sideChainStabilises accumulation of negative charge on the carbonyl oxygen of carbamoyl phosphate during nucleophilic attack by L-ornithine. May accept the proton from the N-delta of L-ornithine.
ArgA319320macie:sideChainStabilises accumulation of negative charge on the carbonyl oxygen of carbamoyl phosphate during nucleophilic attack by L-ornithine.

Annotated By Reference To The Literature - Site 2 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
GlnB136137macie:sideChainStabilises accumulation of positive charge on the N-delta of L-ornithine as this atom attacks the carbonyl of carbamoyl phosphate.
CysB273274macie:sideChainDeprotonates the delta-amino group of L-ornithine to allow it to attack carbamoyl phosphate.
AspB231232macie:sideChainStabilises the thiolate from of the sulfhydryl group of Cys 273, enabling it to accept a proton from L-ornithine.
ArgB106107macie:sideChainStabilises accumulation of negative charge on the carbonyl oxygen of carbamoyl phosphate during nucleophilic attack by L-ornithine.
HisB133134macie:sideChainStabilises accumulation of negative charge on the carbonyl oxygen of carbamoyl phosphate during nucleophilic attack by L-ornithine. May accept the proton from the N-delta of L-ornithine.
ArgB319320macie:sideChainStabilises accumulation of negative charge on the carbonyl oxygen of carbamoyl phosphate during nucleophilic attack by L-ornithine.

Annotated By Reference To The Literature - Site 3 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
GlnC136137macie:sideChainStabilises accumulation of positive charge on the N-delta of L-ornithine as this atom attacks the carbonyl of carbamoyl phosphate.
CysC273274macie:sideChainDeprotonates the delta-amino group of L-ornithine to allow it to attack carbamoyl phosphate.
AspC231232macie:sideChainStabilises the thiolate from of the sulfhydryl group of Cys 273, enabling it to accept a proton from L-ornithine.
ArgC106107macie:sideChainStabilises accumulation of negative charge on the carbonyl oxygen of carbamoyl phosphate during nucleophilic attack by L-ornithine.
HisC133134macie:sideChainStabilises accumulation of negative charge on the carbonyl oxygen of carbamoyl phosphate during nucleophilic attack by L-ornithine. May accept the proton from the N-delta of L-ornithine.
ArgC319320macie:sideChainStabilises accumulation of negative charge on the carbonyl oxygen of carbamoyl phosphate during nucleophilic attack by L-ornithine.

Literature References

Notes:
Shi D
Crystal structure of human ornithine transcarbamylase complexed with carbamoyl phosphate and L-norvaline at 1.9 A resolution.
Proteins 2000 39 271-277
PubMed: 10813810
Jin L
Crystal structure at 2.8 A resolution of anabolic ornithine transcarbamylase from Escherichia coli.
Nat Struct Biol 1997 4 622-625
PubMed: 9253409
Shi D
1.85-A resolution crystal structure of human ornithine transcarbamoylase complexed with N-phosphonacetyl-L-ornithine. Catalytic mechanism and correlation with inherited deficiency.
J Biol Chem 1998 273 34247-34254
PubMed: 9852088
McDowall S
Site-directed mutagenesis of Arg60 and Cys271 in ornithine transcarbamylase from rat liver.
Protein Eng 1990 4 73-77
PubMed: 2290837
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