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Visualization of the Reaction Trajectory and Transition State in a Hydrolytic Reaction Catalyzed by a Metalloenzyme
Author(s) -
Selleck Christopher,
Clayton Daniel,
Gahan Lawrence R.,
Mitić Nataša,
McGeary Ross P.,
Pedroso Marcelo Monteiro,
Guddat Luke W.,
Schenk Gerhard
Publication year - 2017
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201700866
Subject(s) - catalysis , visualization , trajectory , hydrolysis , chemistry , state (computer science) , transition state , combinatorial chemistry , computer science , biochemistry , physics , data mining , algorithm , astronomy
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.