Retrocyclin-2: structural analysis of a potent anti-HIV theta-defensin.

Retrocyclin-2: structural analysis of a potent anti-HIV theta-defensin. Research Abstract Details 

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Retrocyclin-2: structural analysis of a potent anti-HIV theta-defensin. Abstract Text:

Norelle L Daly,Yi-Kuang Chen,K Johan Rosengren,Ute C Marx,Martin L Phillips,Alan J Waring,Wei Wang,Robert I Lehrer,David J Craik,

Retrocyclins are circular mini-defensins with significant potential as agents against human immunodeficiency virus, influenza A, and herpes simplex virus. Retrocyclins bind carbohydrate-containing surface molecules such as gp120 and CD4 with high affinity (Kd, 10-100 nM), promoting their localization on cell membranes. The structural features important for activity have yet to be fully elucidated, but here, we have determined the first three-dimensional structure of a retrocyclin, namely, one of the most potent forms, retrocyclin-2. In the presence of SDS micelles, a well-defined beta-hairpin braced by three disulfide bonds that defines the cystine ladder motif is present. By contrast, a well-defined structure could not be determined in aqueous solution, suggesting that the presence of SDS micelles stabilizes the extended conformation of retrocyclin-2. Translational diffusion measurements indicate that retrocyclin-2 interacts with the SDS micelles, and such a membrane-like interaction may be an important feature in the mechanism of action of these antimicrobial peptides. Analytical ultracentrifugation and the NMR data indicated that retrocyclin-2 self-associates to form a trimer in a concentration-dependent manner. The ability to self-associate may contribute to the high-affinity binding of retrocyclins for glycoproteins by increasing the valency and enhancing the ability of retrocyclins to cross-link cell surface glycoproteins.

Retrocyclin-2: structural analysis of a potent anti-HIV theta-defensin. Publishing Authors By Initials

NL Daly,YK Chen,KJ Rosengren,UC Marx,ML Phillips,AJ Waring,W Wang,RI Lehrer,DJ Craik,

For similar biochemical phenomena, metabolism, and nutrition: biochemical phenomena: structure-activity relationship research abstracts see: biochemical phenomena, metabolism, and nutrition: biochemical phenomena: structure-activity relationship research

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Retrocyclin-2: structural analysis of a potent anti-HIV theta-defensin. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Biochemistry

VOLUME: 46

Page Numbers: 9920-8

Journal Abbreviation: Biochemistry

ISSN: 0006-2960

DAY: 8

MONTH: 08

YEAR: 2007

Retrocyclin-2: structural analysis of a potent anti-HIV theta-defensin. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 370623

Retrocyclin-2: structural analysis of a potent anti-HIV theta-defensin. Keywords Mesh Terms:

KEYWORDS: Structure-Activity Relationship

MESH TERMS: chemistry

Chemical & Substance for Abstract: Retrocyclin-2: structural analysis of a potent anti-HIV theta-defensin. Information

Substance Name: Sodium Dodecyl Sulfate

Registry Number: 151-21-3

Grant and Affiliation Information for Retrocyclin-2: structural analysis of a potent anti-HIV theta-defensin.

AFFILIATION: Institute for Molecular Bioscience and Australian Research Council Special Research Centre for Functional and Applied Genomics, The University of Queensland, Brisbane QLD 4072, Australia.

Country: United States

AGENCY: United States NIAID

GRANT: AI056921

ACRONYM: AI

MEDLINETA: Biochemistry

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ACCESSION NUMBER: 2ATG

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