Crystallization and preliminary X-ray crystallographic analysis of the sclerostin-neutralizing Fab AbD09097.

Abstract

The secreted cystine-knot protein sclerostin was first identified from genetic screening of patients suffering from the rare bone-overgrowth diseases sclerosteosis and van Buchem disease. Sclerostin acts a negative regulator of bone growth through inhibiting the canonical Wnt signalling cascade by binding to and blocking the Wnt co-receptor LRP5/6. Its function in blocking osteoblastogenesis makes it an important target for osteoanabolic therapy approaches to treat osteoporosis, which is characterized by a progressive decrease in bone mass and density. In this work, the production, crystallization and preliminary X-ray diffraction data analysis of a sclerostin-neutralizing human Fab antibody fragment, AbD09097, obtained from a naive antibody library are reported. Crystals of the Fab AbD09097 belonged to space group P21, with unit-cell parameters a = 45.19, b = 78.49, c = 59.20 Å, β = 95.71° and diffracted X-rays to a resolution of 1.8 Å.

• Authors: Verena Boschert, Eva Maria Muth, Achim Knappik, Christian Frisch, Thomas D Mueller
• Journal: Acta crystallographica. Section F, Structural biology communications (Acta Crystallogr F Struct Biol Commun) Vol. 71 Issue Pt 4 Pg. 388-92 (Apr 2015) ISSN: 2053-230X [Electronic] United States
• PMID: 25849496 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adaptor Proteins, Signal Transducing
• Glycoproteins
• Immunoglobulin Fab Fragments
• Immunoglobulin Variable Region
• Intercellular Signaling Peptides and Proteins
• Sost protein, mouse

Topics

• Adaptor Proteins, Signal Transducing
• Amino Acid Sequence
• Animals
• Crystallization
• Crystallography, X-Ray
• Glycoproteins (chemistry, genetics)
• Humans
• Immunoglobulin Fab Fragments (chemistry, genetics)
• Immunoglobulin Variable Region (chemistry, genetics)
• Insecta
• Intercellular Signaling Peptides and Proteins
• Mice
• Molecular Sequence Data