title: Visualization of the Reaction Trajectory and Transition State in a Hydrolytic Reaction Catalyzed by a Metalloenzyme.
abstract: Metallohydrolases are a vast family of enzymes that play crucial roles in numerous metabolic pathways. Several members have emerged as targets for chemotherapeutics. Knowledge about their reaction mechanisms and associated transition states greatly aids the design of potent and highly specific drug leads. By using a high-resolution crystal structure, we have probed the trajectory of the reaction catalyzed by purple acid phosphatase, an enzyme essential for the integrity of bone structure. In particular, the transition state is visualized, thus providing detailed structural information that may be exploited in the design of specific inhibitors for the development of new anti-osteoporotic chemotherapeutics.
authors.affiliation: School of Chemistry and Molecular Biosciences, The University of Queensland, St. Lucia, Queensland, 4072, Australia.
authors.forename: Christopher
authors.initials: C
authors.lastname: Selleck
authors.affiliation: School of Chemistry and Molecular Biosciences, The University of Queensland, St. Lucia, Queensland, 4072, Australia.
authors.forename: Daniel
authors.initials: D
authors.lastname: Clayton
authors.affiliation: School of Chemistry and Molecular Biosciences, The University of Queensland, St. Lucia, Queensland, 4072, Australia.
authors.forename: Lawrence R
authors.initials: LR
authors.lastname: Gahan
authors.affiliation: Department of Chemistry, Maynooth University, Maynooth, Co., Kildare, Ireland.
authors.forename: Nataša
authors.initials: N
authors.lastname: Mitić
authors.affiliation: School of Chemistry and Molecular Biosciences, The University of Queensland, St. Lucia, Queensland, 4072, Australia.
authors.forename: Ross P
authors.initials: RP
authors.lastname: McGeary
authors.affiliation: School of Chemistry and Molecular Biosciences, The University of Queensland, St. Lucia, Queensland, 4072, Australia.
authors.forename: Marcelo Monteiro
authors.initials: MM
authors.lastname: Pedroso
authors.affiliation: School of Chemistry and Molecular Biosciences, The University of Queensland, St. Lucia, Queensland, 4072, Australia.
authors.forename: Luke W
authors.initials: LW
authors.lastname: Guddat
authors.affiliation: School of Chemistry and Molecular Biosciences, The University of Queensland, St. Lucia, Queensland, 4072, Australia.
authors.forename: Gerhard
authors.identifier: http://orcid.org/0000-0001-8619-0631
authors.initials: G
authors.lastname: Schenk
mesh_terms: D000135:Acid Phosphatase / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D055162:Biocatalysis; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D006023:Glycoproteins / Q000737:chemistry / Q000378:metabolism*; D006868:Hydrolysis; D013552:Swine
chemical_list: D006023:Glycoproteins; C091137:purple acid phosphatase; D000135:Acid Phosphatase
keywords: enzymes; hydrolases; metallohydrolases; transition states