2kra

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Solution structure of Bv8Solution structure of Bv8

Structural highlights

2kra is a 1 chain structure with sequence from Bombina variegata. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:Solution NMR, 20 models
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

BV8_BOMVA

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

Bv8, a 77-residue protein isolated from frogs, is the prototypic member of the prokineticin family of cytokines. Prokineticins (PKs) have only recently been identified in vertebrates (including humans), and they are believed to be involved in a number of key physiological processes, such as angiogenesis, neurogenesis, nociception, and tissue development. We used a combination of Boc solid-phase peptide synthesis, native chemical ligation, and in vitro protein folding to establish robust chemical access to this molecule. Synthetic Bv8 was obtained in good yield and exhibited full activity in a human neuroblastoma cell line and rat dorsal root ganglion (DRG) neurons. The 3D structure of the synthetic protein was determined by using NMR spectroscopy and it was found to be homologous with that of mamba intestinal toxin 1, which is the only other known prokineticin structure. Analysis of a truncated mutant lacking five residues at the N terminus that are critical for receptor binding and activation showed no perturbation to the core protein structure. Together with the functional data, this suggests that receptor binding is likely to be a highly cooperative process possibly involving major allosterically driven structural rearrangements. The facile and efficient synthesis presented here will enable preparation of unique chemical analogues of prokineticins, which should be powerful tools for modulating the structure and function of prokineticins and their receptors, and studying the many physiological processes that have been linked to them.

Chemical synthesis and structure of the prokineticin Bv8.,Morales RA, Daly NL, Vetter I, Mobli M, Napier IA, Craik DJ, Lewis RJ, Christie MJ, King GF, Alewood PF, Durek T Chembiochem. 2010 Sep 3;11(13):1882-8. doi: 10.1002/cbic.201000330. PMID:20677202[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

  1. Morales RA, Daly NL, Vetter I, Mobli M, Napier IA, Craik DJ, Lewis RJ, Christie MJ, King GF, Alewood PF, Durek T. Chemical synthesis and structure of the prokineticin Bv8. Chembiochem. 2010 Sep 3;11(13):1882-8. doi: 10.1002/cbic.201000330. PMID:20677202 doi:http://dx.doi.org/10.1002/cbic.201000330
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