4PVD

Crystal structure of yeast methylglyoxal/isovaleraldehyde reductase Gre2 complexed with NADPH

Summary for 4PVD

• Entry DOI: 10.2210/pdb4pvd/pdb
• Related: 4PVC
• Descriptor: NADPH-dependent methylglyoxal reductase GRE2, NADPH DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE (3 entities in total)
• Functional Keywords: rossmann fold, reductase, nadph binding, oxidoreductase
• Biological source: Saccharomyces cerevisiae (yeast)
• Cellular location: Cytoplasm : Q12068
• Total number of polymer chains: 4
• Total formula weight: 154372.58

Authors

Guo, P.C.,Bao, Z.Z.,Li, W.F.,Zhou, C.Z. (deposition date: 2014-03-17, release date: 2014-10-22, Last modification date: 2023-11-08)

Primary citation

Guo, P.C.,Bao, Z.Z.,Ma, X.X.,Xia, Q.,Li, W.F.
Structural insights into the cofactor-assisted substrate recognition of yeast methylglyoxal/isovaleraldehyde reductase Gre2
Biochim.Biophys.Acta, 1844:1486-1492, 2014

PubMed Abstract: Saccharomyces cerevisiae Gre2 (EC1.1.1.283) serves as a versatile enzyme that catalyzes the stereoselective reduction of a broad range of substrates including aliphatic and aromatic ketones, diketones, as well as aldehydes, using NADPH as the cofactor. Here we present the crystal structures of Gre2 from S. cerevisiae in an apo-form at 2.00Å and NADPH-complexed form at 2.40Å resolution. Gre2 forms a homodimer, each subunit of which contains an N-terminal Rossmann-fold domain and a variable C-terminal domain, which participates in substrate recognition. The induced fit upon binding to the cofactor NADPH makes the two domains shift toward each other, producing an interdomain cleft that better fits the substrate. Computational simulation combined with site-directed mutagenesis and enzymatic activity analysis enabled us to define a potential substrate-binding pocket that determines the stringent substrate stereoselectivity for catalysis.

PubMed: 24879127
DOI: 10.1016/j.bbapap.2014.05.008

Experimental method

X-RAY DIFFRACTION (2.4 Å)