4ZP1

Crystal structure of Zymomonas mobilis pyruvate decarboxylase variant Glu473Ala

Summary for 4ZP1

• Entry DOI: 10.2210/pdb4zp1/pdb
• Descriptor: Pyruvate decarboxylase, MAGNESIUM ION, NICKEL (II) ION, ... (6 entities in total)
• Functional Keywords: thiamin diphosphate (thdp), pyruvate decarboxylase, lyase
• Biological source: Zymomonas mobilis
• Total number of polymer chains: 4
• Total formula weight: 245829.21

Authors

Wechsler, C.,Neumann, P.,Tittmann, K. (deposition date: 2015-05-07, release date: 2015-11-04, Last modification date: 2024-05-08)

Primary citation

Wechsler, C.,Meyer, D.,Loschonsky, S.,Funk, L.M.,Neumann, P.,Ficner, R.,Brodhun, F.,Muller, M.,Tittmann, K.
Tuning and Switching Enantioselectivity of Asymmetric Carboligation in an Enzyme through Mutational Analysis of a Single Hot Spot.
Chembiochem, 16:2580-2584, 2015

PubMed Abstract: Enantioselective bond making and breaking is a hallmark of enzyme action, yet switching the enantioselectivity of the reaction is a difficult undertaking, and typically requires extensive screening of mutant libraries and multiple mutations. Here, we demonstrate that mutational diversification of a single catalytic hot spot in the enzyme pyruvate decarboxylase gives access to both enantiomers of acyloins acetoin and phenylacetylcarbinol, important pharmaceutical precursors, in the case of acetoin even starting from the unselective wild-type protein. Protein crystallography was used to rationalize these findings and to propose a mechanistic model of how enantioselectivity is controlled. In a broader context, our studies highlight the efficiency of mechanism-inspired and structure-guided rational protein design for enhancing and switching enantioselectivity of enzymatic reactions, by systematically exploring the biocatalytic potential of a single hot spot.

PubMed: 26488818
DOI: 10.1002/cbic.201500529

Experimental method

X-RAY DIFFRACTION (2.205 Å)