1fjn

From Proteopedia

Revision as of 12:51, 20 November 2007

SOLUTION STRUCTURE AND ACTIVITY OF THE FOUR DISULFIDE BOND MEDITERRANEAN MUSSEL DEFENSIN MGD-1

Overview

MGD-1 is a 39-residue defensin-like peptide isolated from the edible, Mediterranean mussel, Mytilus galloprovincialis. This peptide is, characterized by the presence of four disulfide bonds. We report here its, solid-phase synthesis and an easy way to improve the yield of the four, native disulfide bonds. Synthetic and native MGD-1 display similar, antibacterial activity, suggesting that the hydroxylation of Trp28, observed in native MGD-1 is not involved in the antimicrobial effect. The, three-dimensional solution structure of MGD-1 has been established using, (1)H NMR and mainly consists of a helical part (Asn7-Ser16) and two, antiparallel beta-strands (Arg20-Cys25 and Cys33-Arg37), together giving, rise to the common cystine-stabilized alpha-beta motif frequently observed, in scorpion toxins. In MGD-1, the cystine-stabilized alpha-beta motif is, stabilized by four disulfide bonds (Cys4-Cys25, Cys10-Cys33, Cys14-Cys35, and Cys21-Cys38), instead of by the three disulfide bonds commonly found, in arthropod defensins. Except for the Cys21-Cys38 disulfide bond which is, solvent-exposed, the three others belong to the particularly hydrophobic, core of the highly constrained structure. Moreover, the C4-P5 amide bond, in the cis conformation characterizes the MGD-1 structure. MGD-1 and, insect defensin A possess similar bactericidal anti-Gram-positive, activity, suggesting that the fourth disulfide bond of MGD-1 is not, essential for the biological activity. In agreement with the general, features of antibacterial peptides, the MGD-1 and defensin A structures, display a typical distribution of positively charged and hydrophobic side, chains. The positively charged residues of MGD-1 are located in three, clusters. For these two defensin peptides isolated from insects and, mollusks, it appears that the rather well conserved location of certain, positively charged residues and of the large hydrophobic cluster are, enough to generate the bactericidal potency and the Gram-positive, specificity.

About this Structure

1FJN is a Single protein structure of sequence from [1]. Full crystallographic information is available from OCA.

Reference

Solution structure and activity of the synthetic four-disulfide bond Mediterranean mussel defensin (MGD-1)., Yang YS, Mitta G, Chavanieu A, Calas B, Sanchez JF, Roch P, Aumelas A, Biochemistry. 2000 Nov 28;39(47):14436-47. PMID:11087396

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