1wz9
The 2.1 A structure of a tumour suppressing serpin
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OverviewOverview
Maspin is a serpin that acts as a tumor suppressor in a range of human, cancers, including tumors of the breast and lung. Maspin is crucial for, development, because homozygous loss of the gene is lethal; however, the, precise physiological role of the molecule is unclear. To gain insight, into the function of human maspin, we have determined its crystal, structure in two similar, but non-isomorphous crystal forms, to 2.1- and, 2.8-A resolution, respectively. The structure reveals that maspin adopts, the native serpin fold in which the reactive center loop is expelled fully, from the A beta-sheet, makes minimal contacts with the core of the, molecule, and exhibits a high degree of flexibility. A buried salt bridge, unique to maspin orthologues causes an unusual bulge in the region around, the D and E alpha-helices, an area of the molecule demonstrated in other, serpins to be important for cofactor recognition. Strikingly, the, structural data reveal that maspin is able to undergo conformational, change in and around the G alpha-helix, switching between an open and a, closed form. This change dictates the electrostatic character of a, putative cofactor binding surface and highlights this region as a likely, determinant of maspin function. The high resolution crystal structure of, maspin provides a detailed molecular framework to elucidate the mechanism, of function of this important tumor suppressor.
About this StructureAbout this Structure
1WZ9 is a Single protein structure of sequence from Homo sapiens with SO4 as ligand. Full crystallographic information is available from OCA.
ReferenceReference
The high resolution crystal structure of the human tumor suppressor maspin reveals a novel conformational switch in the G-helix., Law RH, Irving JA, Buckle AM, Ruzyla K, Buzza M, Bashtannyk-Puhalovich TA, Beddoe TC, Nguyen K, Worrall DM, Bottomley SP, Bird PI, Rossjohn J, Whisstock JC, J Biol Chem. 2005 Jun 10;280(23):22356-64. Epub 2005 Mar 10. PMID:15760906
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