Dynamic characterization of the water binding loop in the P-type cardiotoxin: implication for the role of the bound water molecule: Biochemistry

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TypeArticle
Journal titleBiochemistry
Volume40
Issue43
Pages1278212794; # of pages: 13
SubjectAmino Acid Sequence; analysis; Animals; binding; chemistry; Cobra; Consensus Sequence; correlation time; Direct Lytic Factors; DYNAMICS; exchange; Hydrogen; Hydrogen Bonding; lipid; Lipids; Magnetic Resonance Spectroscopy; membrane; Membranes; metabolism; Models,Molecular; Models,Statistical; Models,Theoretical; Molecular Sequence Data; MOLECULE; NMR; NMR analysis; Proline; Protein Binding; Protein Structure,Secondary; Protein Structure,Tertiary; RELAXATION; RESIDUES; Role; SEQUENCE; solvent; structure; Support,Non-U.S.Gov't; surface; Time Factors; Water
AbstractRecent studies of cobra P-type cardiotoxins (CTXs) have shown that the water-binding loop (loop II) plays a crucial role in toxin binding to biological membranes and in their cytotoxicity. To understand the role of bound water in the loop, the structure and dynamics of the major P-type CTX from Taiwan cobra, CTX A3, were determined by a comprehensive NMR analysis involving (1)H NOESY/ROESY, (13)C[1)H]NOE/T(1) relaxation, and (17)O triple-quantum filtered NMR. A single water molecule was found to be tightly hydrogen bonded to the NH of Met26 with a correlation time (5-7 ns) approaching the isotropic tumbling time (3.8-4.5 ns) of the CTX A3 molecule. Surprisingly, despite the relatively long residence time (ca. 5 ns to 100 micros), the bound water molecule of CTX A3 is located within a dynamic (order parameter S(2) approximately 0.7) and solvent accessible loop. Comparison among several P-type CTXs suggests that proline residues in the consensus sequence of MxAxPxVPV should play an important role in the formation of the water binding loop. It is proposed that the exchange rate of the bound water may play a role in regulating the lipid binding mode of amphiphilic CTX molecules near membrane surfaces
Publication date
LanguageEnglish
AffiliationNRC Institute for Biological Sciences; National Research Council Canada
Peer reviewedNo
NRC numberSUE2001
NPARC number9373652
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Record identifierd89c5ba9-12e2-44e6-bd4c-e893824f96de
Record created2009-07-10
Record modified2016-05-09
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