Crystal Structure of the Catalytic Domain of Human ADAM33
Abstract
Adam33 is a putative asthma susceptibility gene encoding for a membrane-anchored metalloprotease belonging to the ADAM family. The ADAMs (a disintegrin and metalloprotease) are a family of glycoproteins implicated in cell-cell interactions, cell fusion, and cell signaling. We have determined the crystal structure of the Adam33 catalytic domain in complex with the inhibitor marimastat and the inhibitor-free form. The structures reveal the polypeptide fold and active site environment resembling that of other metalloproteases. The substrate-binding site contains unique features that allow the structure-based design of specific inhibitors of this enzyme.
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Ntn superfamily members with structures similar to the RoseTTAFold model suggest that TANGO2 functions as an enzyme that might hydrolyze a carbon-nitrogen bond in a membrane component.
“Ntn superfamily members with structures similar to the RoseTTAFold model suggest that TANGO2 functions as an enzyme that might hydrolyze a carbon-nitrogen bond in a membrane component (18).”
From Accurate prediction of protein structures and interactions using a 3-track network (2021) · cites this paper as [18]
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- Authors
- Orth, P., Reichert, P., Wang, W., Prosise, W. W., Yarosh-Tomaine, T., Hammond, G., Ingram, R. N., Xiao, L., Mirza, U. A., Zou, J., Strickland, C., Taremi, S. S., Le, H. V., & Madison, V.
- Corresponding author
- Orth, Peter
- Venue
- Journal of Molecular Biology
- Publisher
- Elsevier BV
- Published
- 2004-01
- Volume
- 335
- Issue
- 1
- Pages
- 129-137
- ISSN
- 0022-2836 (ISSN-L)
- OpenAlex
- W2115301251
- Cited by
- 90
- References
- 23
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 2 · 2023: 1 · 2022: 2 · 2021: 1 · 2020: 2 · 2019: 4 · 2018: 3 · 2017: 5 · 2016: 4 · 2015: 1 · 2013: 2 · 2012: 6
- FWCI
- 2.86
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Molecular Biology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Basic Energy Sciences
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Protease and Inhibitor Mechanisms
- Physical Sciences › Materials Science › Materials Chemistry › Enzyme Structure and Function
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Keywords
- ADAM33, catalytic domain, crystal structure, metalloproteinases, marimastat, asthma susceptibility genes, ADAM family, substrate binding site, active site, enzyme inhibitor design, structure-based drug design
- MeSH terms
- Amino Acid Sequence, Enzyme Inhibitors, Humans, Hydroxamic Acids, Metalloendopeptidases, Models, Molecular, Mutation, Protein Binding, Molecular Structure, Sequence Alignment, Protein Structure, Tertiary, Crystallography, X-Ray, Catalytic Domain, ADAM Proteins
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