Abstract
The significance of BmK CT, a key chlorotoxin-like peptide isolated from the scorpion venom of Buthus martensii Karsch, is a novel blocker of the chloride ion channel and matrix metalloproteinase-2 (MMP-2). Site-directed mutagenesis of BmK CT, wound healing assay, gelatin zymography assay and computational simulation highlight the importance of electrostatic contribution to BmK CT–MMP-2 catalytic domain complex and a model of BmK CT–MMP-2 catalytic domain complex is therefore proposed. This is the first documentation of the structural mechanism of in the inhibition of glioma cell migration by BmK CT and may lead to the molecular design of specific inhibitors of MMP-2.
Similar content being viewed by others
References
Arnold K, Bordoli L, Kopp J, Schwede T (2006) The SWISS-MODEL workspace: A web-based environment for protein structure homology modeling. Bioinformatics 22:195–201
Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE (2000) The protein data bank. Nucleic Acids Res 28:235–242
Chen X, Tong XT, Zhang NX, Wu G, Zhang Q, Wu HM (2005) Solution structure of BmP08, a novel short-chain scorpion toxin from Buthus martensi Karsch. Biochem Biophys Res Commun 330:1116–1126
DeBin JA, Maggio JE, Strichartz GR (1993) Purification and characterization of chlorotoxin, a chloride channel ligand from the venom of the scorpion. Am J Physiol 264:C361–C369
Deshane J, Garner CC, Sontheimer H (2003) Chlorotoxin inhibits glioma cell invasion via matrix metalloproteinase-2. J Biol Chem 278:4135–4144
Falconi M, Altobelli G, Iovino MC, Politi V, Desideri A (2003) Molecular dynamics simulation of matrix metalloproteinase 2: fluctuations and time evolution of recognition pockets. J Comput Aided Mol Des 17:837–848
Fu YJ, Yin LT, Liang AH, Zhang CF, Wang W, Chai BF, Yang JY, Fan XJ (2007) Therapeutic potential of chlorotoxin-like neurotoxin from the Chinese scorpion for human gliomas. Neurosci Lett 412:62–67
Guex N, Peitsch MC (1997) SWISS-MODEL and the Swiss-PdbViewer: An environment for comparative protein modeling. Electrophoresis 18:2714–2723
Kopp J, Schwede T (2004) The SWISS-MODEL Repository of annotated three-dimensional protein structure homology models. Nucleic Acids Res 32:230–234
Lippens G, Najib J, Wodak SJ, Tartar A (1995) NMR sequential assignments and solution structure of chlorotoxin, a small scorpion toxin that blocks chloride channels. Biochemistry 34:13–21
Lu KV, Jong KA, Rajasekaran AK, Cloughesy TF, Mischel PS (2004) Upregulation of tissue inhibitor of metalloproteinases (TIMP)-2 promotes matrix metalloproteinase (MMP)-2 activation and cell invasion in a human glioblastoma cell line. Lab Invest 84:8–20
Mamelak AN, Rosenfeld S, Bucholz R, Raubitschek A, Nabors LB, Fiveash JB, Shen S, Khazaeli MB, Colcher D, Liu A, Osman M, Guthrie B, Schade-Bijur S, Hablitz DM, Alvarez VL, Gonda MA (2006) Phase I single-dose study of intracavitary-administered iodine-131-TM-601 in adults with recurrent high-grade glioma. J Clin Oncol 24:3644–3650
Olsen ML, Schade S, Lyons SA, Amaral MD, Sontheimer H (2003) Expression of voltage-gated chloride channels in human glioma cells. J Neurosci 23:5572–5582
Peitsch MC (1995) Protein modeling by E-mail. Bio/Technology 13658–13660
Pierce B, Weng Z (2005) M-ZDOCK: A grid-based approach for Cn symmetric multimer docking. Bioinformatics 21:1472–1476
Pierce B, Phillips AT, Weng Z (2007) Computational methods for protein structure prediction and modeling: structure prediction. In: Xu Y, Xu D (eds) Structure prediction of protein complexes. Springer, New York, pp 109–134
Schwede T, Kopp J, Guex N, Peitsch MC (2003) SWISS-MODEL: an automated protein homology-modeling server. Nucleic Acids Res 31:3381–3385
Wiehe K, Pierce B, Mintseris J, Tong W, Anderson R, Chen R, Weng Z (2005) ZDOCK and RDOCK performance in CAPRI rounds 3, 4, and 5. Proteins 60:207–213
Wu YL, Cao ZJ, Yi H, Jiang DH, Mao X, Liu H, Li WX (2004) Simulation of the interaction between ScyTx and small conductance calcium-activated potassium channel by docking and MM-PBSA. Biophys J 87:105–112
Zeng XC, Li WX, Zhu SY, Peng F, Zhu ZH, Wu KL, Yang FH (2000) Cloning and characterization of a cDNA sequence encoding the precursor of a chlorotoxin-like peptide from the Chinese scorpion Buthus martensii Karsch. Toxicon 38:1009–1014
Acknowledgments
This project was supported by grants from “National Natural Science Foundation of China (No. 30700534)”, “Natural Science Foundation of Shanxi Province (2008021039)” and “National High Technology Research and Development Program of China (863 Program)”.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Fu, YJ., An, N., Chan, KG. et al. A model of BmK CT in inhibiting glioma cell migration via matrix metalloproteinase-2 from experimental and molecular dynamics simulation study. Biotechnol Lett 33, 1309–1317 (2011). https://doi.org/10.1007/s10529-011-0587-7
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10529-011-0587-7