The Biochemistry and Structural Biology Lab.
Kuo-Long Lou, Ph.D
Associate Professor of Biochemistry and Structural Biology
Graduate Institute of Oral Biology, School of Dentistry, College of Medicine / Institute of Biochemistry and Molecular Biology, College of Medicine / Institute of Biotechnology, College of Bio-Resources and Agriculture / Center for biotechnology, National Taiwan University / R.O.C.
Office Tel: +886-2-23123456 ext. 66616
Office Fax: +886-2-23820685
1987 Department of Environmental Engineering National Cheng-Kung University/R.O.C. (B.S.)
1989 Institute of Biological Chemistry National Cheng-Kung University/R.O.C. (M.S.)
1993 Department of Structural Biology, Biozentrum University of Basel/ Switzerland (M.A.)
1996 Department of Structural Biology, Biozentrum University of Basel/S witzerland (Ph.D.)
1991-1992 Institute of Biology III University of Freiburg/ Germany (T.A.)
1992-1996 Department of Structural Biology, Biozentrum University of Basel/ Switzerland (T.A.)
1996 Department of Structural Biology, Biozentrum University of Basel/ Switzerland (Postdoc)
1997-1999 Department of Medical Physiology and Biophysics/ Neurosciences Research Groups, Faculty of Medicine, University of Calgary/ Canada (Research Associate)
1999-2003 Graduate Institute of Oral Biology/ Medical College / National Taiwan University (Assistant Professor)
2002- Institute of Biochemistry and Molecular Biology / Medical College/ National Taiwan University (Joint Appointment)
2008- Institute of Biotechnology/ Bio-Resources and Agriculture College/ National Taiwan University (Joint Appointment)
2009- Center for Biotechnology/ National Taiwan University (Joint Appointment)
The research of Dr. Kuo-Long Lou has been recently focused on the studies of structure and functional regulations of potassium channels. These studies are mainly based upon the structural analysis in combination with biochemical and electrophysiological methods applied to develop the gating mechanisms of potassium channels in nanoscales or in atomic levels. Meanwhile, through the approach via toxin-channel interactions, Dr. Lou has proposed several novel theoretical hypotheses and therefore expanded the collaborations with other institutions both inside and outside the university.
Huang, P. T., Shiau Y. S. & Lou K. L.* (2007). The Interaction of Spider Gating Modifier Peptides with Voltage-Gated Potassium Channels. Toxicon. 49, 285-292.
The structure-functional study of potassium channel regulations. We combine biochemistry, structural biology, bioinformatics, and cellular electrophysiology to approach and to investigate the molecular mechanism of Kir channel regulations (ROMK1 and KATP) and Kv channel gating. (in collaboration with pharmacology department).
(A) Toxin-channel interactions. The hanatoxins and other toxins, are investigated with facilities of synchrotron radiations. (international collaborations with Academia Sinica, NSRRC, pharmacology, Bragg Institutes and Sidney Univ.) In addition, regarding the molecular mechanism of binding-induced inhibition of gating in voltage-dependent K+-channels by hanatoxin, molecular docking simulations revealed significant conformational change of S3C segment in the structure of S3C-hanatoxin complex, which has been comprehended as a reasonable factor resulting in the inhibition of channel activation not through blocking directly on the pore. Further experiments with biochemical and kinetic methods, e.g., stopped-flow technique and fluorescence titration, were used to verify such hypothesis.
Lou et al. (2002) J. Mol. Recognit. 15, 175-179
Huang et al. (2002) Recept. Channels 8, 79-85
Shiau et al. (2002) J. Mol. Model. 8, 243-247
Lou et al. (2003) J. Mol. Recognit. 16, 392-395
Shiau et al. (2003) Chem. Res. Toxicol. 16, 1217-1225
Huang et al. (2007). Toxicon 49, 285-292.
(B) Expression, purification and crystallization of Kir6.2 and the intracellular domains of Kir1.1 channels.
Lou et al. (2001) J. Mol. Model. 7, 20-25
Kung et al. (2008) J. Formos. Med. Assoc. 107, 600-608
Lee et al. (2008) J. Mol. Graph. Model. 27, 332-341
(C) Structural analysis of the unique insecticidal activity of VrD1 (VrCRP) targeting on potassium channels and the homoplasy evolutionary links between plant defensins and arthropod neurotoxins. Methodology used includes mutational/electrophysiological analyses, proteomics, SAXS, and SANS (for membrane interaction detection, see also below).The toxin-membrane interactions. A novel plant defensin VrD1 is applied in the search of membrane target(s), whereas the interactions between biomembranes and VrD1, as well as hanatoxins and other toxins, are investigated with facilities of synchrotron radiations. (international collaborations with Academia Sinica, NSRRC, pharmacology, Bragg Institutes and Sidney Univ.)
Shiau et al. (2006) J. Mol. Recognit. 19, 441-450
(D) The functional roles of potassium channels on masticatory muscle fatigue.
Shiau et al. (2003) J. Oral Rehabil. 30, 978-984.
(E) Structural study of caries proteins. (in collaboration with microbiology and dentistry departments) This includes the 3-D structural analysis of S. mutans glucosyltransferases. Update results of putative but constructive structural evidence have demonstrated and implied the possible mechanism of the reduced GTF enzyme activities due to monoclonal antibody recognition.
Tsai et al. (2000) FEMS Microbiol. Lett. 188, 75-79
Chia et al. (2003) J. Mol. Model. 9, 153-158
(F) Development of Software for virtual drug screening and structural studies. Practical software will be shortly free and online available for academic purposes.
(G) Crystal structural analysis for the interactions of (membrane) proteins involved in carcinogenesis mechanism induced by Helicobacter pylori (including SAXS). (in collaboration with biochemistry department)
(H) Structural and functional characterizations of haemostatic/thrombolytic proteins (in angiogenesis). This study includes the Ca2+-induced conformational change and the dimerization of human thrombomodulin domains and the formation of ternary complex of Streptokinase-plasmin-plasminogen. (international collaborations with NCKU, biochemistry department, medical technology dept., NSRRC, and Sidney Univ.) Expression, purification and crystallization of various TM domains are also underway.
(I) Development of crystallization methods. (in collaboration with physics department)