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An Interdisciplinary Research Centre at the University of Cambridge


Prof. Hendrik van Veen is a professor of molecular pharmacology (grade 11) and principal investigator focussing on the structure-function relationships in bacterial multidrug transporters that underlie their ability to recognise different antibiotics and mediate metabolic energy-dependent drug extrusion. He also focuses on mechanisms of inhibition of these efflux pumps, and on the interactions of multidrug transporters with 'natural' substrates, such as lipids, that can define alternative physiological roles of these transport systems. His lab uses several different sources of information in their research efforts, including pharmacology, microbiology, biochemistry, biophysics and structural biology.


Multidrug transporters are important contributors to the intrinsic and acquired antimicrobial resistance that can be encountered during drug-based therapies in a clinical setting. In the VanVeen group, the interactions between bacterial multidrug transporters and drugs are analysed in transport measurements in intact cell and membrane vesicles, and in proteoliposomes and nanodiscs containing purified proteins. Drug binding is also assessed in equilibrium binding assays with radiolabelled ligands and in fluorescence anisotropy and tryptophan fluorescence assays. Electrophysiological techniques are used to study electrogenic substrate transport reactions in planar lipid bilayers. We also incorporate protein crystallography, NMR, EPR, and mass spectrometry through collaborations with others. Hence, the group integrates a wide range of molecular techniques in research on the mechanisms of multidrug transporters. See for further information about our research interests and projects.


Key publications: 

Van Veen, H.W., Venema, K., Bolhuis, B., Oussenko, I., Kok, J., Poolman, B., Driessen, A.J.M., and Konings, W.N. (1996) Multidrug resistance mediated by a bacterial homolog of the human drug transporter MDR1. Proc. Natl. Acad. Sci. USA 93: 10668-10672.

Van Veen, H.W., Callaghan, R., Soceneantu, L., Sardini, A., Konings, W.N., and Higgins, C.F. (1998) A bacterial antibiotic-resistance gene that complements the human multidrug-resistance P-glycoprotein gene. Nature 391: 291-295.

Putman, M., Koole, L., Van Veen, H.W., and Konings, W.N. (1999) The secondary multidrug transporter LmrP contains multiple drug interaction sites. Biochemistry 38: 13900-13905.

Van Veen, H.W., Margolles, A., Müller, M., Higgins, C.F., and Konings, W.N. (2000) The ATP-binding cassette transporter LmrA mediates multidrug transport by an alternating two-site (two-cylinder engine) mechanism. EMBO J. 19: 2503-2514.

Venter, H., Shilling, R., Velamakanni, S., Balakrishnan, L., and Van Veen, H.W. (2003) An ABC transporter with a secondary-active multidrug translocator domain. Nature 426: 866-869.

Reuter, G., Janvilisri, T., Venter, H., Shahi, S., Balakrishnan, L., and Van Veen, H.W. (2003) The ATP-binding cassette multidrug transporter LmrA and lipid transporter MsbA have overlapping substrate specificities. J. Biol. Chem 278: 35193-35198.

Balakrishnan, L., Venter, H., Shilling, R.A., and Van Veen, H.W. (2004) Reversible transport by the ATP-binding cassette multidrug export pump LmrA: ATP synthesis at the expense of downhill ethidium uptake. J. Biol. Chem. 279: 11273-11280.

Woebking, B., Velamakanni, S., Federici, L., Seeger, M.A., Murakami, S., and Van Veen, H.W. (2008) Functional role of transmembrane helix 6 in drug binding and transport by the ABC transporter MsbA. Biochemistry 47: 10904-10914.

Barrera, N.P., Isaacson, S.C., Zhou, M., Bavro, V.N., Welch, A., Schaedler, T.A., Seeger, M.A., Miguel, R.N., Korkhov, V.M., van Veen, H.W., Venter, H., Walmsley, A.R., Tate, C.G., Robinson, C.V. (2009) Mass spectrometry of membrane transporters reveals subunit stoichiometry and interactions. Nature Methods 6(8):585-587.

Van Veen, H.W. (2010) Structural biology: Last of the multidrug transporters. Nature 467: 926-927.

Schaedler, T.A., and Van Veen, H.W. (2010) A flexible cation binding site in the multidrug major facilitator superfamily transporter LmrP is associated with variable proton coupling. FASEB J. 24: 3653-3661.

Doshi, R., Ali, A., Shi, W., Freeman, E.V., Fagg, L.A., van Veen, H.W. (2013) Molecular disruption of the power stroke in the ATP-binding cassette transport protein MsbA. J Biol Chem. 288(10):6801-6813.

Choudhury*, H.G., Tong*, Z., Mathavan, I., Li, Y., Iwata, S., Zirah, S., Rebuffat, S., Van Veen, H.W., and Beis, K. (2014) Structure of an antibacterial peptide ATP-binding cassette transporter in a novel outward occluded state. Proc. Natl. Acad. Sci. USA. 111: 9145-9150. (* shared first authors)

Jin, Y., Nair, A., and Van Veen, H.W. (2014) Multidrug transport protein NorM from Vibrio cholerae simultaneously couples to sodium- and proton-motive force. J. Biol. Chem. 289(21): 14624-14632

Singh, H., Velamakanni, S., Deery, M.J., Howard, J., Wei, S.L., and Van Veen, H.W. (2016) ATP-dependent substrate transport by the ABC transporter MsbA is proton-coupled. Nature Commun. 7, 12387 doi: 10.1038/ncomms12387.

Fitzpatrick, A. W. P., Llabrés, S., Neuberger, A., Blaza, J.N., Bai, X.C., Okada, U., Murakami, S., van Veen, H.W., Zachariae, U., Scheres, S.H.W., Luisi, B.F., Du, D. (2017) Structure of the MacAB-TolC ABC-type tripartite multidrug efflux pump. Nature Microbiol. 2:17070. doi: 10.1038/nmicrobiol.2017.70.

Okada, U., Yamashita, E., Neuberger, A., Morimoto, M., van Veen, H.W., Murakami, S. (2017) Crystal structure of tripartite-type ABC transporter MacB from Acinetobacter baumannii. Nature Commun. 8(1):1336.   doi: 10.1038/ s41467-017-01399-2.

Du, D., Wang-Kan, X., Neuberger, A., van Veen, H.W., Pos, K.M., Piddock, L.J.V., Luisi, B.F. (2018) Multidrug efflux pumps: structure, function and regulation. Nature Reviews Microbiol. doi: 10.1038/s41579-018-0048-6.

Agboh, K., Lau, C.H.F., Khoo, Y.S.K., Singh, H., Raturi, S., Nair, A.V., Howard, J., Chiapello, M., Feret, R., Deery, M.J., Murakami, S., van Veen, H.W. (2018) Powering the ABC multidrug exporter LmrA: How nucleotides embrace the ion-motive force. Science Advances 4, eaas9365.

Raturi, S., Nair, A. V., Shinoda, K., Singh, H., Bai, B., Murakami, S., Fujitani, H., van Veen, H. W. (2021) Engineered MATE multidrug transporters reveal two functionally distinct ion-coupling pathways in NorM from Vibrio cholerae. Commun. Biol. 4: 558.

Professor of Molecular Pharmacology (grade 11)
Focus on Antimicrobial Resistance research
Dr Hendrik W.  van Veen

Contact Details

Department of Pharmacology
Tennis Court Road
Takes PhD students
Available for consultancy


Departments and institutes: 
Person keywords: 
Drug Resistance
Antimicrobial resistance
Structural Biology
Drug Discovery