4DD8

ADAM-8 metalloproteinase domain with bound batimastat

4DD8 の概要

• エントリーDOI: 10.2210/pdb4dd8/pdb
• 分子名称: Disintegrin and metalloproteinase domain-containing protein 8, 4-(N-HYDROXYAMINO)-2R-ISOBUTYL-2S-(2-THIENYLTHIOMETHYL)SUCCINYL-L-PHENYLALANINE-N-METHYLAMIDE, CALCIUM ION, ... (8 entities in total)
• 機能のキーワード: batimastat, inflammation, alpha/beta motif, metalloproteinase, allergic asthma, tumorigenesis, arthritis, aberrant neural cell signaling, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Membrane; Single-pass type I membrane protein: P78325
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 96153.62

構造登録者

Hall, T.,Shieh, H.S.,Day, J.E.,Caspers, N.,Chrencik, J.E.,Williams, J.M.,Pegg, L.E.,Pauley, A.M.,Moon, A.F.,Krahn, J.M.,Fischer, D.H.,Kiefer, J.R.,Tomasselli, A.G.,Zack, M.D. (登録日: 2012-01-18, 公開日: 2012-06-06, 最終更新日: 2024-11-06)

主引用文献

Hall, T.,Shieh, H.S.,Day, J.E.,Caspers, N.,Chrencik, J.E.,Williams, J.M.,Pegg, L.E.,Pauley, A.M.,Moon, A.F.,Krahn, J.M.,Fischer, D.H.,Kiefer, J.R.,Tomasselli, A.G.,Zack, M.D.
Structure of human ADAM-8 catalytic domain complexed with batimastat.
Acta Crystallogr.,Sect.F, 68:616-621, 2012

PubMed 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 β-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.

PubMed: 22684055
DOI: 10.1107/S1744309112015618

実験手法

X-RAY DIFFRACTION (2.1 Å)