1hvz
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(New page: 200px<br /><applet load="1hvz" size="450" color="white" frame="true" align="right" spinBox="true" caption="1hvz" /> '''RTD-1, A CYCLIC ANTIMICROBIAL DEFENSIN FROM ...)
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Revision as of 01:01, 25 November 2007
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RTD-1, A CYCLIC ANTIMICROBIAL DEFENSIN FROM RHESUS MACAQUE LEUKOCYTES
Overview
Most mammalian defensins are cationic peptides of 29-42 amino acids long, stabilized by three disulfide bonds. However, recently Tang et al. (1999, Science 286, 498-502) reported the isolation of a new defensin type found, in the leukocytes of rhesus macaques. In contrast to all the other, defensins found so far, rhesus theta defensin-1 (RTD-1) is composed of, just 18 amino acids with the backbone cyclized through peptide bonds., Antibacterial activities of both the native cyclic peptide and a linear, form were examined, showing that the cyclic form was 3-fold more active, than the open chain analogue [Tang et al. (1999) Science 286, 498-502]. To, elucidate the three-dimensional structure of RTD-1 and its open chain, analogue, both peptides were synthesized using solid-phase peptide, synthesis and tert-butyloxycarbonyl chemistry. The structures of both, peptides in aqueous solution were determined from two-dimensional (1)H NMR, data recorded at 500 and 750 MHz. Structural constraints consisting of, interproton distances and dihedral angles were used as input for, simulated-annealing calculations and water refinement with the program, CNS. RTD-1 and its open chain analogue oRTD-1 adopt very similar, structures in water. Both comprise an extended beta-hairpin structure with, turns at one or both ends. The turns are well defined within themselves, and seem to be flexible with respect to the extended regions of the, molecules. Although the two strands of the beta-sheet are connected by, three disulfide bonds, this region displays a degree of flexibility. The, structural similarity of RTD-1 and its open chain analogue oRTD-1, as well, as their comparable degree of flexibility, support the theory that the, additional charges at the termini of the open chain analogue rather than, overall differences in structure or flexibility are the cause for oRTD-1's, lower antimicrobial activity. In contrast to numerous other antimicrobial, peptides, RTD-1 does not display any amphiphilic character, even though, surface models of RTD-1 exhibit a certain clustering of positive charges., Some amide protons of RTD-1 that should be solvent-exposed in monomeric, beta-sheet structures show low-temperature coefficients, suggesting the, possible presence of weak intermolecular hydrogen bonds.
About this Structure
1HVZ is a Single protein structure of sequence from [1]. Full crystallographic information is available from OCA.
Reference
Three-dimensional structure of RTD-1, a cyclic antimicrobial defensin from Rhesus macaque leukocytes., Trabi M, Schirra HJ, Craik DJ, Biochemistry. 2001 Apr 10;40(14):4211-21. PMID:11284676
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