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Structure of human ADAM-8 catalytic domain complexed with batimastat.

ABSTRACT: The role of ADAM-8 in cancer and inflammatory diseases such as allergy, arthritis and asthma makes it an attractive target for drug development. Therefore, the catalytic domain of human ADAM-8 was expressed, purified and crystallized in complex with a hydroxamic acid inhibitor, batimastat. The crystal structure of the enzyme-inhibitor complex was refined to 2.1 Å resolution. ADAM-8 has an overall fold similar to those of other ADAM members, including a central five-stranded ?-sheet and a catalytic Zn(2+) ion. However, unique differences within the S1' binding loop of ADAM-8 are observed which might be exploited to confer specificity and selectivity to ADAM-8 competitive inhibitors for the treatment of diseases involving this enzyme.

SUBMITTER: Hall T

PROVIDER: S-EPMC3370895 | biostudies-literature | 2012 Jun

REPOSITORIES: biostudies-literature

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Structure of human ADAM-8 catalytic domain complexed with batimastat.

Hall Troii T Shieh Huey Sheng HS Day Jacqueline E JE Caspers Nicole N Chrencik Jill E JE Williams Jennifer M JM Pegg Lyle E LE Pauley Adele M AM Moon Andrea F AF Krahn Joseph M JM Fischer David H DH Kiefer James R JR Tomasselli Alfredo G AG Zack Marc D MD

Acta crystallographica. Section F, Structural biology and crystallization communications 20120522 Pt 6

The role of ADAM-8 in cancer and inflammatory diseases such as allergy, arthritis and asthma makes it an attractive target for drug development. Therefore, the catalytic domain of human ADAM-8 was expressed, purified and crystallized in complex with a hydroxamic acid inhibitor, batimastat. The crystal structure of the enzyme-inhibitor complex was refined to 2.1 Å resolution. ADAM-8 has an overall fold similar to those of other ADAM members, including a central five-stranded β-sheet and a catalyt ...[more]

PMID: 22684055

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