4DD8

ADAM-8 metalloproteinase domain with bound batimastat

Summary for 4DD8

• Entry DOI: 10.2210/pdb4dd8/pdb
• Descriptor: 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)
• Functional Keywords: batimastat, inflammation, alpha/beta motif, metalloproteinase, allergic asthma, tumorigenesis, arthritis, aberrant neural cell signaling, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Homo sapiens (human)
• Cellular location: Membrane; Single-pass type I membrane protein: P78325
• Total number of polymer chains: 4
• Total formula weight: 96153.62

Authors

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. (deposition date: 2012-01-18, release date: 2012-06-06, Last modification date: 2024-11-06)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.1 Å)