1lp3

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1lp3, resolution 3.0Å

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The Atomic Structure of Adeno-Associated Virus (AAV-2), a Vector for Human Gene Therapy

Overview

The structure of the adeno-associated virus (AAV-2) has been determined to, 3-A resolution by x-ray crystallography. AAV is being developed as a, vector for gene therapy to treat diseases including hemophilia, cancer, and cystic fibrosis. As in the distantly related autonomous parvoviruses, the capsid protein has a beta-barrel fold, but long loops between the, beta-strands share little structural homology with other parvoviruses, leading to unique surface features. Most prominent are groups of, threefold-related peaks, each an intimate association of loops from two, neighboring subunits. Mutations affecting cell entry and receptor binding, are clustered near the positively charged side of each peak, implicating, the region in attachment to the cellular receptor, heparan sulfate, proteoglycan. Amino acids involved in antibody binding are in the same, general vicinity. The structure will guide rational engineering of vector, capsids to tailor cellular targeting and to avoid immediate neutralization, by an immune system sensitized by prior exposure to AAV.

About this Structure

1LP3 is a Single protein structure of sequence from Adeno-associated virus 2. Full crystallographic information is available from OCA.

Reference

The atomic structure of adeno-associated virus (AAV-2), a vector for human gene therapy., Xie Q, Bu W, Bhatia S, Hare J, Somasundaram T, Azzi A, Chapman MS, Proc Natl Acad Sci U S A. 2002 Aug 6;99(16):10405-10. Epub 2002 Jul 22. PMID:12136130

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