title: Structure-Activity Relationship of Chlorotoxin-Like Peptides.
abstract: Animal venom (e.g., scorpion) is a rich source of various protein and peptide toxins with diverse physio-/pharmaco-logical activities, which generally exert their action via target-specific modulation of different ion channel functions. Scorpion venoms are among the most widely-known source of peptidyl neurotoxins used for callipering different ion channels, such as; Na⁺, K⁺, Ca⁺, Cl(-), etc. A new peptide of the chlorotoxin family (i.e., Bs-Tx7) has been isolated, sequenced and synthesized from scorpion Buthus sindicus (family Buthidae) venom. This peptide demonstrates 66% with chlorotoxin (ClTx) and 82% with CFTR channel inhibitor (GaTx1) sequence identities reported from Leiurus quinquestriatus hebraeus venom. The toxin has a molecular mass of 3821 Da and possesses four intra-chain disulphide bonds. Amino acid sequence analysis of Bs-Tx7 revealed the presence of a scissile peptide bond (i.e., Gly-Ile) for human MMP2, whose activity is increased in the case of tumour malignancy. The effect of hMMP2 on Bs-Tx7, or vice versa, observed using the FRET peptide substrate with methoxycoumarin (Mca)/dinitrophenyl (Dnp) as fluorophore/quencher, designed and synthesized to obtain the lowest Km value for this substrate, showed approximately a 60% increase in the activity of hMMP2 upon incubation of Bs-Tx7 with the enzyme at a micromolar concentration (4 µM), indicating the importance of this toxin in diseases associated with decreased MMP2 activity.
authors: International Center for Chemical and Biochemical Sciences (ICCBS), HEJ Research Institute of Chemistry, University of Karachi, Karachi-75270, Pakistan. abid.ali@iccs.edu.|Interfaculty Institute of Biochemistry (IIB), University of Tuebingen, Hoppe-Seyler Str. 4, Tuebingen D-72076, Germany. abid.ali@iccs.edu.|Venom Evolution Laboratory, School of Biological Sciences, University of Queensland, Brisbane, QLD 4072, Australia. abid.ali@iccs.edu.
authors: Syed Abid
authors: SA
authors: Ali
authors: International Center for Chemical and Biochemical Sciences (ICCBS), HEJ Research Institute of Chemistry, University of Karachi, Karachi-75270, Pakistan. promet213@yahoo.com.|Interfaculty Institute of Biochemistry (IIB), University of Tuebingen, Hoppe-Seyler Str. 4, Tuebingen D-72076, Germany. promet213@yahoo.com.
authors: Mehtab
authors: M
authors: Alam
authors: International Center for Chemical and Biochemical Sciences (ICCBS), HEJ Research Institute of Chemistry, University of Karachi, Karachi-75270, Pakistan. atiya786@super.net.pk.
authors: Atiya
authors: A
authors: Abbasi
authors: Venom Evolution Laboratory, School of Biological Sciences, University of Queensland, Brisbane, QLD 4072, Australia. e.undheim@uq.edu.au.
authors: Eivind A B
authors: EA
authors: Undheim
authors: Venom Evolution Laboratory, School of Biological Sciences, University of Queensland, Brisbane, QLD 4072, Australia. bgfry@uq.edu.au.
authors: Bryan Grieg
authors: BG
authors: Fry
authors: Interfaculty Institute of Biochemistry (IIB), University of Tuebingen, Hoppe-Seyler Str. 4, Tuebingen D-72076, Germany. kalbacher@uni-tuebingen.de.
authors: Hubert
authors: H
authors: Kalbacher
authors: Interfaculty Institute of Biochemistry (IIB), University of Tuebingen, Hoppe-Seyler Str. 4, Tuebingen D-72076, Germany. Wolfgang.Voelter@uni-tuebingen.de.
authors: Wolfgang
authors: W
authors: Voelter
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D060829:Arthropod Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D010455:Peptides / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D011487:Protein Conformation; D012604:Scorpion Venoms / Q000737:chemistry*; D013329:Structure-Activity Relationship
chemical_list: D060829:Arthropod Proteins; D010455:Peptides; D012604:Scorpion Venoms; C091539:Chlorotoxin; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2
keywords: CFTR; MMP2; chloride channel; chlorotoxin; peptidyl-inhibitors; scorpion venom