2Q99

Crystal Structure of Saccharopine Dehydrogenase from Saccharomyces cerevisiae

Summary for 2Q99

• Entry DOI: 10.2210/pdb2q99/pdb
• Descriptor: Saccharopine dehydrogenase [NAD+, L-lysine-forming (2 entities in total)
• Functional Keywords: dehydrogenase, alpha-aminoadipate pathway, fungal lysine synthesis, alpha/beta protein, rossmann fold, oxidoreductase
• Biological source: Saccharomyces cerevisiae (baker's yeast)
• Cellular location: Cytoplasm : P38998
• Total number of polymer chains: 1
• Total formula weight: 42317.17

Authors

Berghuis, A.M.,Burk, D.L. (deposition date: 2007-06-12, release date: 2007-11-06, Last modification date: 2024-11-20)

Primary citation

Burk, D.L.,Hwang, J.,Kwok, E.,Marrone, L.,Goodfellow, V.,Dmitrienko, G.I.,Berghuis, A.M.
Structural Studies of the Final Enzyme in the alpha-Aminoadipate Pathway-Saccharopine Dehydrogenase from Saccharomyces cerevisiae
J.Mol.Biol., 373:745-754, 2007

PubMed Abstract: The 1.64 A structure of the apoenzyme form of saccharopine dehydrogenase (SDH) from Saccharomyces cerevisiae shows the enzyme to be composed of two domains with similar dinucleotide binding folds with a deep cleft at the interface. The structure reveals homology to alanine dehydrogenase, despite low primary sequence similarity. A model of the ternary complex of SDH, NAD, and saccharopine identifies residues Lys77 and Glu122 as potentially important for substrate binding and/or catalysis, consistent with a proton shuttle mechanism. Furthermore, the model suggests that a conformational change is required for catalysis and that residues Lys99 and Asp281 may be instrumental in mediating this change. Analysis of the crystal structure in the context of other homologous enzymes from pathogenic fungi and human sources sheds light into the suitability of SDH as a target for antimicrobial drug development.

PubMed: 17854830
DOI: 10.1016/j.jmb.2007.08.044

Experimental method

X-RAY DIFFRACTION (1.64 Å)