A single histidine residue modulates enzymatic activity in acidic mammalian chitinase

Anton P. Bussink; Jocelyne Vreede; Johannes M. F. G. Aerts; Rolf G. Boot

doi:10.1016/j.febslet.2008.02.032

A single histidine residue modulates enzymatic activity in acidic mammalian chitinase

Anton P. Bussink
, Jocelyne Vreede
, Johannes M. F. G. Aerts
, Rolf G. Boot

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Mammals express two active chitinases, chitotriosidase and AMCase. Only AMCase displays an extremely acidic pH optimum, consistent with its observed presence in the gastrointestinal 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. (C) 2008 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved

Original language	English
Pages (from-to)	931-935
Journal	FEBS letters
Volume	582
Issue number	6
DOIs	https://doi.org/10.1016/j.febslet.2008.02.032
Publication status	Published - 2008

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title = "A single histidine residue modulates enzymatic activity in acidic mammalian chitinase",

abstract = "Mammals express two active chitinases, chitotriosidase and AMCase. Only AMCase displays an extremely acidic pH optimum, consistent with its observed presence in the gastrointestinal 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. (C) 2008 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved",

author = "Bussink, \{Anton P.\} and Jocelyne Vreede and Aerts, \{Johannes M. F. G.\} and Boot, \{Rolf G.\}",

year = "2008",

doi = "10.1016/j.febslet.2008.02.032",

language = "English",

volume = "582",

pages = "931--935",

journal = "FEBS letters",

issn = "0014-5793",

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T1 - A single histidine residue modulates enzymatic activity in acidic mammalian chitinase

AU - Bussink, Anton P.

AU - Vreede, Jocelyne

AU - Aerts, Johannes M. F. G.

AU - Boot, Rolf G.

PY - 2008

Y1 - 2008

N2 - Mammals express two active chitinases, chitotriosidase and AMCase. Only AMCase displays an extremely acidic pH optimum, consistent with its observed presence in the gastrointestinal 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. (C) 2008 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved

AB - Mammals express two active chitinases, chitotriosidase and AMCase. Only AMCase displays an extremely acidic pH optimum, consistent with its observed presence in the gastrointestinal 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. (C) 2008 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved

U2 - 10.1016/j.febslet.2008.02.032

DO - 10.1016/j.febslet.2008.02.032

M3 - Article

C2 - 18294964

SN - 0014-5793

VL - 582

SP - 931

EP - 935

JO - FEBS letters

JF - FEBS letters

IS - 6

ER -

A single histidine residue modulates enzymatic activity in acidic mammalian chitinase

Abstract

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