3SZA

Crystal structure of human ALDH3A1 - apo form

Summary for 3SZA

• Entry DOI: 10.2210/pdb3sza/pdb
• Related: 3SZ9 3SZB
• Descriptor: Aldehyde dehydrogenase, dimeric NADP-preferring, POTASSIUM ION, ACETATE ION, ... (4 entities in total)
• Functional Keywords: aldh, rossmann fold, oxidoreductase
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm : P30838
• Total number of polymer chains: 2
• Total formula weight: 104765.96

Authors

Khanna, M.,Hurley, T.D. (deposition date: 2011-07-18, release date: 2011-11-02, Last modification date: 2023-09-13)

Primary citation

Khanna, M.,Chen, C.H.,Kimble-Hill, A.,Parajuli, B.,Perez-Miller, S.,Baskaran, S.,Kim, J.,Dria, K.,Vasiliou, V.,Mochly-Rosen, D.,Hurley, T.D.
Discovery of a novel class of covalent inhibitor for aldehyde dehydrogenases.
J.Biol.Chem., 286:43486-43494, 2011

PubMed Abstract: Human aldehyde dehydrogenases (ALDHs) comprise a family of 17 homologous enzymes that metabolize different biogenic and exogenic aldehydes. To date, there are relatively few general ALDH inhibitors that can be used to probe the contribution of this class of enzymes to particular metabolic pathways. Here, we report the discovery of a general class of ALDH inhibitors with a common mechanism of action. The combined data from kinetic studies, mass spectrometric measurements, and crystallographic analyses demonstrate that these inhibitors undergo an enzyme-mediated β-elimination reaction generating a vinyl ketone intermediate that covalently modifies the active site cysteine residue present in these enzymes. The studies described here can provide the basis for rational approach to design ALDH isoenzyme-specific inhibitors as research tools and perhaps as drugs, to address diseases such as cancer where increased ALDH activity is associated with a cellular phenotype.

PubMed: 22021038
DOI: 10.1074/jbc.M111.293597

Experimental method

X-RAY DIFFRACTION (1.48 Å)