3q2r | pdb_00003q2r
crystal structure of sGLIPR1 soaked with zinc chloride
Structural highlights
FunctionPublication Abstract from PubMedHuman glioma pathogenesis-related protein 1 (GLIPR1) is a membrane protein that is highly upregulated in brain cancers but is barely detectable in normal brain tissue. GLIPR1 is composed of a signal peptide that directs its secretion, a conserved cysteine-rich CAP (cysteine-rich secretory proteins, antigen 5 and pathogenesis-related 1 proteins) domain and a transmembrane domain. GLIPR1 is currently being investigated as a candidate for prostate cancer gene therapy and for glioblastoma targeted therapy. Crystal structures of a truncated soluble domain of the human GLIPR1 protein (sGLIPR1) solved by molecular replacement using a truncated polyalanine search model of the CAP domain of stecrisp, a snake-venom cysteine-rich secretory protein (CRISP), are presented. The correct molecular-replacement solution could only be obtained by removing all loops from the search model. The native structure was refined to 1.85 A resolution and that of a Zn(2+) complex was refined to 2.2 A resolution. The latter structure revealed that the putative binding cavity coordinates Zn(2+) similarly to snake-venom CRISPs, which are involved in Zn(2+)-dependent mechanisms of inflammatory modulation. Both sGLIPR1 structures have extensive flexible loop/turn regions and unique charge distributions that were not observed in any of the previously reported CAP protein structures. A model is also proposed for the structure of full-length membrane-bound GLIPR1. Structural studies of human glioma pathogenesis-related protein 1.,Asojo OA, Koski RA, Bonafe N Acta Crystallogr D Biol Crystallogr. 2011 Oct;67(Pt 10):847-55. Epub 2011, Sep 8. PMID:21931216[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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