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Triad of polar residues implicated in pH specificity of acidic mammalian chitinase.

ABSTRACT: Acidic mammalian chitinase (AMCase) is a mammalian chitinase that has been implicated in allergic asthma. One of only two active mammalian chinases, AMCase, is distinguished from other chitinases by several unique features. Here, we present the novel structure of the AMCase catalytic domain, both in the apo form and in complex with the inhibitor methylallosamidin, determined to high resolution by X-ray crystallography. These results provide a structural basis for understanding some of the unique characteristics of this enzyme, including the low pH optimum and the preference for the beta-anomer of the substrate. A triad of polar residues in the second-shell is found to modulate the highly conserved chitinase active site. As a novel target for asthma therapy, structural details of AMCase activity will help guide the future design of specific and potent AMCase inhibitors.

SUBMITTER: Olland AM 

PROVIDER: S-EPMC2760363 | biostudies-literature | 2009 Mar

REPOSITORIES: biostudies-literature

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Triad of polar residues implicated in pH specificity of acidic mammalian chitinase.

Olland Andrea M AM   Strand James J   Presman Eleonora E   Czerwinski Robert R   Joseph-McCarthy Diane D   Krykbaev Rustem R   Schlingmann Gerhard G   Chopra Rajiv R   Lin Laura L   Fleming Margaret M   Kriz Ron R   Stahl Mark M   Somers William W   Fitz Lori L   Mosyak Lidia L  

Protein science : a publication of the Protein Society 20090301 3

Acidic mammalian chitinase (AMCase) is a mammalian chitinase that has been implicated in allergic asthma. One of only two active mammalian chinases, AMCase, is distinguished from other chitinases by several unique features. Here, we present the novel structure of the AMCase catalytic domain, both in the apo form and in complex with the inhibitor methylallosamidin, determined to high resolution by X-ray crystallography. These results provide a structural basis for understanding some of the unique  ...[more]

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