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The Wolf-Watz NMR-lab

The basic paradigm in structural biology is that protein function is dictated by the three-dimensional structure. However, under cellular conditions, time dependent fluctuations of protein structures (dynamics) and temporal interactions with other macromolecules (such as proteins, nucleic acids and membranes) are indispensable for functionality. In my laboratory we investigate the relation between protein structure and dynamics to function. Our main experimental technique is high resolution protein NMR spectroscopy in solution. However, complementary techniques such as protein engineering, circular dichroism, isothermal titration calorimetry, molecular dynamics simulations and functional assays are integrated and essential in our research. We have three main research interests: (1) The role of enzyme dynamics in enzymatic catalysis, (2) Structure and dynamics of proteins that control infectivity in the bacterium Yersinia pseudotuberculosis, and (3) Interactions between chaperones and folded protein substrates .

Open position

We have an opening for a two-year postdoctoral fellowship in protein NMR, dead-line for application is first of September, 2013. Please call or email to inquire.

Key words NMR, enzyme, dynamics, function, mechanism


Enzyme dynamics Structural flexibility is many cases intimately linked to the function of proteins and enzymes. Traditionally enzyme mechanisms have been deciphered by combining knowledge from static structures and kinetic measurements. In my lab we are interested in the time-dependent fluctuations of the enzyme and the coupling between fluctuations and function.


Figure 1. A conformational pre-existing equilibrium in substrate-free AK can be perturbed by either mutation (blue contours) or addition of an osmolyte (purple contours). The catalytic parameters kcat and KM are modulated based on the magnitude of Kconf (JACS, 2012).

One of the fundamental requirements for the viability of cellular organisms is that cellular chemical reactions occur on a time scale that is much faster than the turnover rate of global processes (such as cell division). This requirement is accomplished by the action of enzymes that are extraordinary biocatalysts accelerating chemical reactions. To accomplish their tasks enzymes have to perform several complex tasks; (i) binding of substrates weakly enough to avoid kinetic traps; (ii) extremely tight binding to the transition state compound; (iii) activation of functional groups on the substrate(s); (iv) optimal alignment of substrates to facilitate the chemical transformation into products and (v) dehydration of active sites. All these tasks are dependent on structural changes of the enzyme occurring on time-scales optimized for its biological function. In my lab we are interested in the time-dependent fluctuations of enzymes and the coupling between fluctuations and function. Adenylate kinase (AK) has emerged as one of the principal model systems to study the interplay between structure, dynamics and enzymatic activity. We have made several contributions to the understanding of conformational dynamics and activity by using the AK system. For example, we have recently shown that the magnitude of a pre-existing conformational equilibrium in AK modulates the catalytic parameters kcat and KM (JACS, 2012). We have also found that the mechanism of conformational change in response to ATP binding follow a "order-disorder-order" mechanism where specific segments unfold before refolding into the closed and active state (Nature Communications, 2010). In our most recent contribution (Biochemistry, 2013) we have identified the structural topology of an initial equilibrium complex between AK and ATP. It was found that ATP is partially activated already in this transient complex. We are continuing our efforts in the field both with AK and another kinase working on small substrates.

Protein structure and dynamics in bacterial infections

Pathogenicity of the bacterium Yersinia pseudotuberculosis is dependent on translocation of effector proteins into eukaryotic host cells. The translocation process is accomplished with a multi-protein complex called the type III secretion system. Translocation is highly regulated and we study the structure and dynamics of proteins that are key regulatory players. One of our targets is YscU that is a membrane protein with a soluble cytosolic domain. Interestingly the soluble domain undergoes auto-proteolysis at a conserved NPTH motif. We have recently shown (PLoS ONE, 2012) that dissociation of the two folded polypeptides in YscU and secretion of the C-terminal polypeptide is crucial for effector protein secretion. We are continuing our reserach on YscU and also of a number of other proteins , all of which gives well-dispersed NMR spectra of high quality.


Figure 2. Secretion of effector proteins in Yersinia pseudotuberculosis is dependent on dissociation of YscUc into its two polypeptides (PLoS ONE, 2012). The irreversible dissociation kinetics was quantified with NMR for wild-type (black) and a gain of function mutant (red).

Chaperones, structure and interaction with folded substrates

In this project we are investigating two different aspects of chaperone function at the molecular level; (i) the role of heat shock proteins in bacterial pathogenicity and (ii) the structure and function of chaperones involved in transport of E. coli outer membrane proteins through the periplasmatic space.

Bruker 500 MHz spectrometer
Bruker 600 MHz spectrometer with cryoprobe
Bruker 850 MHz spectrometer with cryoprobe

Lab members
Per Rogne, postdoc. per.rogne@chem.umu.se
Michael Kovermann, postdoc. michael.kovermann@chem.umu.se
Ho Ngoc Hoang Oanh, phD student, oanh.ho@chem.umu.se


Xavier Salvatella, Institute for Research in Biomedicine, Barcelona Spain.

Alexander Schug, Steinbuch Centre for Computing, Karlsruhe Institute of Technologie, Germany.

Daniel Daley, Department of Biochemistry and Biophysics, Stockholm University, Sweden.

Hans Wolf-Watz, Department of Molecular Biology, Umeå University, Sweden

Contact Information
Magnus Wolf-Watz,
Associate professor, Department of Chemistry
Department of Chemistry
Umeå University
SE-901 87
Office phone: +46-90-786 7690
Lab phone: +46-90-786 6576




År sorteringsordning


Kovermann, Michael
Grundström, Christin
Sauer-Eriksson, A. Elisabeth; et al.

Structural basis for ligand binding to an enzyme by a conformational selection pathway
Proceedings of the National Academy of Sciences of the United States of America, 114(24): 6298-6303



Ho, Oanh
Rogne, Per
Edgren, Tomas; et al.

Characterization of the Ruler Protein Interaction Interface on the Substrate Specificity SwitchProtein in the Yersinia Type III Secretion System
Journal of Biological Chemistry, 292(8): 3299-3311



Kovermann, Michael
Rogne, Per
Wolf-Watz, Magnus

Protein dynamics and function from solution state NMR spectroscopy
Quarterly reviews of biophysics (Print), 49



Rogne, Per
Wolf-Watz, Magnus

Urea-Dependent Adenylate Kinase Activation following Redistribution of Structural States
Biophysical Journal, 111(7): 1385-1395



Tükenmez, Hasan
Magnussen, Helge
Kovermann, Michael; et al.

Linkage between Fitness of Yeast Cells and Adenylate Kinase Catalysis
PLoS ONE, 11(9)



Perdersen, Martin Nors
Fodera, Vito
Horvath, Istvan; et al.

Direct Correlation Between Ligand-Induced alpha-Synuclein Oligomers and Amyloid-like Fibril Growth
Scientific Reports, 5



Wolf-Watz, Magnus
Kovermann, Michael

Dynamics of a Naturally Hidden State Restricts Adenylate Kinase Activity
Biophysical Journal, 108(2): 30A-30A



Kovermann, Michael
Ådén, Jörgen
Grundström, Christin; et al.

Structural basis for catalytically restrictive dynamics of a high-energy enzyme state
Nature Communications, 6



Rogne, Per
Sparrman, Tobias
Anugwom, Ikenna; et al.

Real-time 31P NMR investigation on the catalytic behavior of the enzyme Adenylate kinase in the matrix of a switchable ionic liquid
ChemSusChem, 8(2): 3764-3768



Esteban-Martin, Santiago
Fenwick, Robert Bryn
Ådén, Jörgen; et al.

Correlated Inter-Domain Motions in Adenylate Kinase
PloS Computational Biology, 10(7): e1003721-



Sidansvarig: Magnus Wolf-Watz