title: The structure of phosphate-bound Escherichia coli adenylosuccinate lyase identifies His171 as a catalytic acid.
abstract: Adenylosuccinate lyase (ASL) is an enzyme from the purine-biosynthetic pathway that catalyzes the cleavage of 5-aminoimidazole-4-(N-succinylcarboxamide) ribonucleotide (SAICAR) to 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) and fumarate. ASL is also responsible for the conversion of succinyladenosine monophosphate (SAMP) to adenosine monophosphate (AMP) and fumarate. Here, the crystal structure of adenylosuccinate lyase from Escherichia coli was determined to 1.9 A resolution. The enzyme adopts a substrate-bound conformation as a result of the presence of two phosphate ions bound in the active site. Comparison with previously solved structures of the apoenzyme and an SAMP-bound H171A mutant reveals a conformational change at His171 associated with substrate binding and confirms the role of this residue as a catalytic acid.
authors.affiliation: Department of Biochemistry, McGill University, Montreal, Quebec, Canada.
authors.forename: Guennadi
authors.initials: G
authors.lastname: Kozlov
authors.forename: Long
authors.initials: L
authors.lastname: Nguyen
authors.forename: Jessica
authors.initials: J
authors.lastname: Pearsall
authors.forename: Kalle
authors.initials: K
authors.lastname: Gehring
mesh_terms: D000143:Acids; D000264:Adenylosuccinate Lyase / Q000737:chemistry*; D055162:Biocatalysis; D018360:Crystallography, X-Ray; D004926:Escherichia coli / Q000201:enzymology*; D006639:Histidine / Q000378:metabolism*; D010710:Phosphates / Q000378:metabolism*; D017433:Protein Structure, Secondary; D021122:Protein Subunits / Q000737:chemistry; D013379:Substrate Specificity
chemical_list: D000143:Acids; D010710:Phosphates; D021122:Protein Subunits; D006639:Histidine; D000264:Adenylosuccinate Lyase