(1) The research fields of Dr. Kuo-Long Lou have been recently focusing in 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 for the activation or inhibition mechanisms of potassium channels in nanoscales or atomic levels. Meanwhile, through the approach by way of toxin-channel interactions, Dr. Lou has proposed several novel theoretical hypotheses regarding this and therefore expanded the collaboration with other institutions both inside and outside the university.
(A) Molecular mechanism of binding-induced inhibition on gating of 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 in aspects of biochemical and kinetic studies, e.g., stopped-flow and fluorescence titration, are underway to verify such hypothesis. A series of results regarding this have led to publications listed below:
(1) Molecular determinants of the hanatoxin binding in voltage-gated K+- channel drkl.J Mol Recognit 15. 175-179, 2002. (2) Structural influence of hanatoxin binding on the carboxyl terminus of S3 segment in voltage-gated K(+)-channel Kv2.1. Recept Channels 8:79-85, 2002.
(3) Molecular simulation reveals structural determinants of the hanat`oxin binding in Kv2.1 channels. J Mol Model 8: 253-257, 2002.
(4) A possible molecular mechanism of hanatoxin binding-modified gating in voitage-gated Kc-channels. J Mol Recognit 16: 392-395, 2003.
(5) Structural basis of binding and inhibition of novel tarantula toxins in mammalian voltage-dependent potassium channels. Chem Res Toxicol 16: 1217-1225, 2003.
(B) Expression, purification and crystallization of Kir6.2 and the intracellular domains of Kirl.l channels. Related work was published in Involvement of a novel C-terminal kinase domain of Kir6.2 in the K-ATP channel rundown
reactivation. JMol Model 7: 20-25, 2001.
(C) Structural and evolutionary analyses of the unique insecticidal activity of VrD1 (VrCRP) targeting on potassium channels and the homoplasy evolutionary link between plant defensins and arthropod neurotoxins.
(D) The functional roles of potassium channels on masticatory muscle fatigue. Pioneering and related studies published in
(1)The effects of masseter muscle pain on biting performance. J Oral Rehabil 30: 978-984, 2003
(2) Depressor effect on blood pressure and flow elicited by electroacupuncture in normal subjects. Auton Neurosci 107: 60-64, 2003
(E) Structural and functional interpretations of GTFs (human caries proteins):updated data in putative but constructive structural evidence have demonstrated and implied the possible mechanism of the reduced enzyme activity due to monoclonal antibody recognition. Publication:
(1) Three-dimensional modelling of the catalytic domain of Streptococcus mutans glucosyltransferase GtfB. FEMS
Microbiol Lett 188. 75-79, 2000.
(2) Structural analysis of the functional influence of the surface peptide Gtf-P1 on Streptococcus mutans glucosyltransferase C activity. J Mol Model.9:153-158,2003.
(2) Assistant Professor Chang Bei-En's research focused on Teratogenic effect of arecoiine: we studey developmentally toxic effects of arecoline, the major aikaloid in the betel nut, in zebrafish. The results showed that arecoline exerts developmenially toxic effects by generally lowering the embryo weight and retarding development of the embryo. The results have been published in Birth Defects Research (Part A) 70:28 -36, 2004.