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| | ==The 2.8 A structure of a tumour suppressing serpin== | | ==The 2.8 A structure of a tumour suppressing serpin== |
| - | <StructureSection load='1xu8' size='340' side='right' caption='[[1xu8]], [[Resolution|resolution]] 2.80Å' scene=''> | + | <StructureSection load='1xu8' size='340' side='right'caption='[[1xu8]], [[Resolution|resolution]] 2.80Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1xu8]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1XU8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1XU8 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1xu8]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1XU8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1XU8 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.8Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">SERPINB5 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1xu8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1xu8 OCA], [http://pdbe.org/1xu8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1xu8 RCSB], [http://www.ebi.ac.uk/pdbsum/1xu8 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1xu8 ProSAT]</span></td></tr> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1xu8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1xu8 OCA], [https://pdbe.org/1xu8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1xu8 RCSB], [https://www.ebi.ac.uk/pdbsum/1xu8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1xu8 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/SPB5_HUMAN SPB5_HUMAN]] Tumor suppressor. It blocks the growth, invasion, and metastatic properties of mammary tumors. As it does not undergo the S (stressed) to R (relaxed) conformational transition characteristic of active serpins, it exhibits no serine protease inhibitory activity. | + | [https://www.uniprot.org/uniprot/SPB5_HUMAN SPB5_HUMAN] Tumor suppressor. It blocks the growth, invasion, and metastatic properties of mammary tumors. As it does not undergo the S (stressed) to R (relaxed) conformational transition characteristic of active serpins, it exhibits no serine protease inhibitory activity. |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | ==See Also== | | ==See Also== |
| - | *[[Serpin|Serpin]] | + | *[[Serpin 3D structures|Serpin 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Bashtannyk-Puhalovich, T A]] | + | [[Category: Large Structures]] |
| - | [[Category: Irving, J A]] | + | [[Category: Bashtannyk-Puhalovich TA]] |
| - | [[Category: Kim, N]] | + | [[Category: Irving JA]] |
| - | [[Category: Law, R H]] | + | [[Category: Kim N]] |
| - | [[Category: Rossjohn, J]] | + | [[Category: Law RH]] |
| - | [[Category: Ruzyla, K]] | + | [[Category: Rossjohn J]] |
| - | [[Category: Whisstock, J C]] | + | [[Category: Ruzyla K]] |
| - | [[Category: Worrall, D M]] | + | [[Category: Whisstock JC]] |
| - | [[Category: Maspin]]
| + | [[Category: Worrall DM]] |
| - | [[Category: Serpin]]
| + | |
| - | [[Category: Serpinb5]]
| + | |
| - | [[Category: Signaling protein]]
| + | |
| - | [[Category: Tumor suppressor]]
| + | |
| Structural highlights
Function
SPB5_HUMAN Tumor suppressor. It blocks the growth, invasion, and metastatic properties of mammary tumors. As it does not undergo the S (stressed) to R (relaxed) conformational transition characteristic of active serpins, it exhibits no serine protease inhibitory activity.
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
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.
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[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ 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. The high resolution crystal structure of the human tumor suppressor maspin reveals a novel conformational switch in the G-helix. J Biol Chem. 2005 Jun 10;280(23):22356-64. Epub 2005 Mar 10. PMID:15760906 doi:http://dx.doi.org/10.1074/jbc.M412043200
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