Molecular Functions, Catalysis and Regulation

Beilstein Enzymology Symposium 2019

10– 12 September, 2019

Hotel Jagdschloss Niederwald, Rüdesheim, Germany

Scientific Committee:

Barbara Bakker / University of Groningen
Santiago Schnell / University Michigan
Thomas S. Ley / The Albert Einstein College of Medicine, New York
Ming-Daw Tsai / Academia Sinica, Taipei
Carsten Kettner / Beilstein-Institut

The Beilstein Enzymology Symposium 2019 brought together biochemists, enzymologists and systems biologists with experts in bioinformatics and computer sciences.

Topics 2019

insights into the activity of macromolecules using cryo-EM
regulation and control of information transfer
lipid metabolism, nutrition and diseases
pseudoenzymes - evolution and transformation of protein function

cofactors in metabolism and regulation
systems biology and metabolic pathway analysis
computational biology

Overview

In enzymology, catalytic reactions usually are investigated in vitro under well-defined conditions which may mimic physiological conditions. This experimental design allows the characterization of the kinetic capabilities of enzymes and to draw conclusions on both the mechanisms of the conversion of substrates into products and the effect of co-enzymes, essential metal ions and modifiers on the structure of the enzyme and thus on the overall catalytic reaction. In addition to biochemical methods, optical methods have emerged to study protein-structure function. In particular, cryogenic electron microscopy (cryo-EM) has led to new insights of the structures of large protein complexes at near-atomic resolution whose 3D models reveal how these molecules function in the cell.

However, the single-enzyme kinetics obtained under in vitro conditions may be misleading if this data is transferred into in vivo conditions due to the high viscosity in the cell. The cellular environment is densely packed with macromolecules such as proteins, RNA, DNA and metabolites which form ‘quinary’ interactions mediated by repulsing and attracting electrostatic forces. In particular, for metabolic pathways in which multi-step reactions are catalyzed this requires either a close spatial arrangement of the enzymes involved (and which has been proposed a substrate channeling for e.g. glycolysis) or lowered turnover rate through the pathway due to increased diffusion times for the individual substrates. Thus, the spatial and temporal arrangement of enzymes has to be regulated to achieve the necessary pathway efficiency, especially for those being located in the cytoplasm. In addition, pathway kinetics is highly controlled by modifying effectors e.g. the diverse types of inhibition and activation of individual enzymes.

This Symposium takes molecular functions, catalysis and regulation in perspective and addresses the insights in structure-function relationships using cryo-EM and computational biology, the role of cofactors in metabolism and regulation, and systems-wide analysis of metabolic pathways.

The Beilstein Enzymology Symposia embrace structural, computational and biological disciplines, and bring researchers (established and younger workers) together to discuss the many and diverse roles of enzymes in biology, and to explore the limits and challenges of holistic studies that attempt to integrate microscopic views of protein function into complex biological behaviour.

Under the guidance of the STRENDA Commission (www.beilstein-strenda.org), this conference series also provides a platform to present the results of this working group’s efforts, to discuss about the requirements for setting up standards in biochemistry and to address the needs making research data findable, accessible, interoperable and reusable. The mission of STRENDA is to establish guidelines for the reliable and accurate reporting of protein function data, and to maintain a database (STRENDA DB, www.beilstein-strenda-db.org) which stores this data after its validation on completeness and compliance with the STRENDA Guidelines.

We have seen many committed discussions about the latest results, approaches and methodologies presented in experimental, theoretic and bioinformatics enzymology.

Scientific Program

Tuesday, 10 Sept.

9.00
Opening and Introductory Remarks
Carsten Kettner

Session Chair: Hans V. Westerhoff

9.20
New Horizons in Enzymology from Cryo-EM and X-ray Free-electron Laser (XFEL)
Ming-Daw Tsai

9.55
Single Molecule Enzymology and Beyond
Xiaoliang Sunney Xie

10.30
Poster Flash Presentation #1

11.00
Coffee Break and Poster Session

11.30
Common Mechanisms by Skeletal Muscle Actomyosin and Bacterial Flagellar Motor Revealed by Electron Cryomicroscopy and Optical Nanophotometry
Keiichi Namba

12.05
Structures of Flexible Membrane Proteins are Best Solved Cold
Alexander Hahn

12.40
Lunch

Session Chair: Barbara M. Bakker

14.00
Analysis of Allosteric Interactions in a Multi-enzyme Complex by Ancestral Sequence Reconstruction
Reinhard Sterner

14.35
Coenzyme A from Extracellular Sources and the Impact thereof in Health and Disease
Ody Sibon

15.10
Tea Break and Conference Photo

15.40
Emerging Concepts in Pseudoenzyme Evolution and Cell Signalling
Patrick Eyers

16.15
STYX: a Pseudophosphatase that Regulates MAPK Signalling and SCF Ubiquitin Ligases via Spatial Anchoring
Hesso Farhan

16.50
Noise and Irreproducibility in Biochemistry
Hans V. Westerhoff

17.30
Close

19.30
Dinner

Wednesday, 11 Sept.

Session Chair: Polly Fordyce

9.00
EMBL-EBI Bioinformatic Infrastructure Provision: Protein Function, Network Biology, Modelling and Beyond
Rolf Apweiler

9.35
Modelling the Minimal Cell: Integration of Experiments, Theory and Simulations
Zaida Luthey-Schulten

10.10
Quantum Chemistry as a Tool in Biocatalysis
Fahmi Himo

10.45
Coffee Break and Poster Session

11.15
Half-Site Enzymes as Conduits for the Transfer of Chemical Potential
Thomas S. Leyh

11.50
The Role of Active Site Loops in Controlling Catalysis by the Aromatic Amino Acid Hydroxylases
Paul F. Fitzpatrick

12.25
Enzymology of Lignin Degradation
Frank M. Raushel

13.00
Lunch

14.15
Excursion

19.30
Dinner

Thursday, 12 Sept.

Session Chair: Ody Sibon

9.00
Are Peroxygenases the New P450s? Scope and Current Challenges of Peroxygenases for Selective Oxyfunctionalisation Chemistry
Frank Hollmann

9.35
The NAD Metabolome – Enzymology and Subcellular Compartmentation
Mathias Ziegler

10.10
Identifying Evolutionary and Kinetic Drivers of NAD-dependend Signalling
Ines Heiland

10.45
Coffee Break

11.15
From Enzymes to Products: Automating Synthetic Biology Routes to Chemical Targets
Neil Swainston

11.50
HT-MEK: a New Microfluidic Platform for Quantitative, High-throughput Enzymology
Polly Fordyce

12.25
Lunch

Session Chair: Paul F. Fitzpatrick

13.40
The Conserved Myosin 1D Controls Muliscale Chirality in Drosophila
Stéphane Noselli

14.15
Computational Modelling of Cerebral Amino Acid and Neurotransmitter Metabolism in Phenylketonuria
Barbara M. Bakker

14.50
Tea Break

15.20
Data Integrated Simulation of Enzymes
Jürgen Pleiss

15.55
The Uncertainty of the Michaelis Constant, K_M, in Experimental Reproducible Enzyme Kinetic Public Data
Santiago Schnell

16.30
STRENDA DB - Monitoring the Completeness of Experimental Enzyme Kinetics Data
Johann M. Rohwer

Discussion

17.15
Closing Remarks
Carsten Kettner

19.30
Dinner