6CSJ

Structure of a Bacillus coagulans polyol dehydrogenase double mutant with an acquired D-lactate dehydrogenase activity

Summary for 6CSJ

• Entry DOI: 10.2210/pdb6csj/pdb
• Descriptor: Glycerol dehydrogenase (2 entities in total)
• Functional Keywords: polyol dehydrogenase, oxidoreductase
• Biological source: Bacillus coagulans
• Total number of polymer chains: 8
• Total formula weight: 314895.78

Authors

Hurlbert, J.C.,St.John, F.J. (deposition date: 2018-03-20, release date: 2019-07-03, Last modification date: 2023-10-04)

Primary citation

Chauliac, D.,Wang, Q.,St John, F.J.,Jones, G.,Hurlbert, J.C.,Ingram, L.O.,Shanmugam, K.T.
Kinetic characterization and structure analysis of an altered polyol dehydrogenase with d-lactate dehydrogenase activity.
Protein Sci., 29:2387-2397, 2020

PubMed Abstract: During adaptive metabolic evolution a native glycerol dehydrogenase (GDH) acquired a d-lactate dehydrogenase (LDH) activity. Two active-site amino acid changes were detected in the altered protein. Biochemical studies along with comparative structure analysis using an X-ray crystallographic structure model of the protein with the two different amino acids allowed prediction of pyruvate binding into the active site. We propose that the F245S alteration increased the capacity of the glycerol binding site and facilitated hydrogen bonding between the S245 γ-O and the C1 carboxylate of pyruvate. To our knowledge, this is the first GDH to gain LDH activity due to an active site amino acid change, a desired result of in vivo enzyme evolution.

PubMed: 33020946
DOI: 10.1002/pro.3963

Experimental method

X-RAY DIFFRACTION (2.395 Å)