UW Medicine Division of Allergy and Infectious Diseases
Directory >> Wilhelmus G. J. Hol, PhD

Faculty

Wilhelmus G. J. Hol, PhD

  • Professor of Biochemistry
  • University of Washington

Wim Hol is interested in protein crystallography for structure-based design of drugs for tropical diseases. The major goals of our laboratory are to unravel the three-dimensional structures of key protein molecules, to explore the relationships among protein structure, function, and dynamics, and to exploit this insight for the design of new medically relevant molecules, in particular for the treatment of infectious tropical diseases. This includes

  1. We have recently solved the high-resolution structures of three editosome proteins from the sleeping sickness parasite Trypanosoma brucei: the RNA-editing ligase (REL1),the RNA-editing terminal uridylyl transferase (RET2), and the key structural protein "A6" which keeps the multi-million Dalton complex together.
  2. In our research on cholera toxin and heat-labile enterotoxin, we recently have solved over 20 crystal structures of 10 different protein components from the large Type 2 Secretion System (T2SS), which translocates the toxins from the periplasm into the lumen of the human host.
  3. For understanding the host cell invasion machinery of the malaria parasite, the structures of the Plasmodium falciparum MyoA-tail with the MyoA tail interaction protein (MTIP) has been very informative, and forms the basis of structure-based design of new anti-malaria compounds with collaborators in the Departments of Biochemistry and Medicine. Within the framework of the Medical Structural Genomics of pathogenic Protozoa (MSGPP) program project we have solved numerous structures of potential drug target proteins from Plasmodium, Trypanosoma, Leishmania, Toxoplasma and Cryptosporidium species. On the basis of these studies low nanomolar inhibitors of these parasites in cell assays have already been obtained.

Selected Publications


Korotkov KV, Gray MD, Kreger A, Turley S, Sandkvist M, Hol WG. Calcium is essential for the major pseudopilin in the type 2 secretion system. J Biol Chem. 2009 Sep 18;284(38):25466-70.
[The following link will open in a new window. PubMed Abstract ]


Abendroth J, Kreger AC, Hol WG. The dimer formed by the periplasmic domain of EpsL from the Type 2 Secretion System of Vibrio parahaemolyticus. J Struct Biol. 2009 Nov;168(2):313-22..
[ The following link will open in a new window. PubMed Abstract ]


Korotkov KV, Pardon E, Steyaert J, Hol WG.Crystal structure of the N-terminal domain of the secretin GspD from ETEC determined with the assistance of a nanobody. Structure. 2009 Feb 13;17(2):255-65.
[ The following link will open in a new window. PubMed Abstract ]


Amaro, R. E., Schnaufer, A., Interthal, H., Hol, W. G. J., Stuart, K. & McCammon, J. A. (2008) Discovery of drug-like inhibitors of an essential RNA-editing ligase in Trypanosoma brucei. PNAS. 2008 November 11; 105(45): 17278–17283.
[The following link will open in a new window. PNAS - accessed August 16, 2010. ]


Korotkov KV, Hol WG. Structure of the GspK-GspI-GspJ complex from the enterotoxigenic Escherichia coli type 2 secretion system. Nat Struct Mol Biol. 2008 May;15(5):462-468.
[The following link will open in a new window. PubMed Abstract ]


Bosch J, Turley S, Roach CM, Daly TM, Bergman LW, Hol WG. The closed MTIP-myosin A-tail complex from the malaria parasite invasion machinery. J Mol Biol. 2007 Sep 7;372(1):77-88.
[The following link will open in a new window. PubMed Abstract ]

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