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A single histidine residue modulates enzymatic activity in acidic mammalian chitinase
Author(s) -
Bussink Anton P.,
Vreede Jocelyne,
Aerts Johannes M.F.G.,
Boot Rolf G.
Publication year - 2008
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2008.02.032
Subject(s) - chitinase , histidine , active site , residue (chemistry) , biochemistry , enzyme , chemistry , biology , biophysics
Mammals express two active chitinases, chitotriosidase and AMCase. Only AMCase displays an extremely acidic pH optimum, consistent with its observed presence in the gastro‐intestinal tract. A structural model of AMCase reveals the presence of a conserved histidine residue in the active site. Mutational analyses and molecular dynamics simulations show that His187 is responsible for the acidic optimum and suggest pH dependent modulation of the reaction mechanism that is unique to AMCases. Concluding, His187 is a crucial structural component of the active site of AMCase and this unique feature may serve as a lead for the development of specific inhibitors.