# Selected Publications

### Small-molecule inhibition of pyruvate phosphate dikinase targeting the nucleotide binding site

Pyruvate phosphate dikinase (PPDK) is an essential enzyme of C4 photosynthesis in plants, catalyzing the ATP-driven conversion of pyruvate to phosphoenolpyruvate (PEP). It is further used by some bacteria and unicellular protists in the reverse, ATP-forming direction. Many weed species use C4 photosynthesis in contrast to world’s major crops, which are C3 plants. Hence inhibitors of PPDK may be used as C4-specific herbicides. By screening a library of 80 commercially available kinase inhibitors, we identified compounds derived from bisindolylmaleimide (bisindolylmaleimide IV, IC50 = 0.76 ± 0.13 μM) and indirubin (indirubin-3’-monoxime, IC50 = 4.2 ± 0.9 μM) that showed high inhibitory potency towards PPDK and are among the most effective PPDK inhibitors described today. Physiological studies on leaf tissues of a C4 model plant confirmed in vivo inhibition of C4-driven photosynthesis by these substances. Moreover, comparative docking studies of non-inhibitory bisindolylmaleimide derivatives suggest that the selectivity towards PPDK may be increased by addition of functional groups to the core structure.
In PLOS ONE, 2017.

### Structural intermediates and directionality of the swiveling motion of Pyruvate Phosphate Dikinase

Pyruvate phosphate dikinase (PPDK) is a vital enzyme in cellular energy metabolism catalyzing the ATP- and Pi-dependent formation of phosphoenolpyruvate from pyruvate in C4 -plants, but the reverse reaction forming ATP in bacteria and protozoa. The multi-domain enzyme is considered an efficient molecular machine that performs one of the largest single domain movements in proteins. However, a comprehensive understanding of the proposed swiveling domain motion has been limited by not knowing structural intermediates or molecular dynamics of the catalytic process. Here, we present crystal structures of PPDKs from Flaveria, a model genus for studying the evolution of C4 -enzymes from phylogenetic ancestors. These structures resolve yet unknown conformational intermediates and provide the first detailed view on the large conformational transitions of the protein in the catalytic cycle. Independently performed unrestrained MD simulations and configurational free energy calculations also identified these intermediates. In all, our experimental and computational data reveal strict coupling of the CD swiveling motion to the conformational state of the NBD. Moreover, structural asymmetries and nucleotide binding states in the PPDK dimer support an alternate binding change mechanism for this intriguing bioenergetic enzyme.
In Sci Rep, 2017.

# Recent Publications

. Ensemble- and rigidity theory-based perturbation approach to analyze dynamic allostery. In J Chem Theory Comput, 2017.

. eLabFTW: An open source laboratory notebook for research labs. In JOSS, 2017.

. Structural intermediates and directionality of the swiveling motion of Pyruvate Phosphate Dikinase. In Sci Rep, 2017.

# Projects

#### C4 Photosynthesis

C4 plants are characterized by their ability to thrive in warm and dry environments by efficient usage of nitrogen, water and CO2

#### eLabFTW

A free and open source electronic lab notebook.

# Privacy Statement

This site does not track its visitors. IP addresses will be logged in anonymized form for administrative purposes only. In this process, the last octet is removed from the address (e.g. 136.77.167.15 will become 136.77.167.0). Additionally, log files are deleted regularly in an automated manner.

If you have any questions regarding privacy issues, please do not hesitate to contact me.