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| | ==Structure of ulilysin mutant M290L== | | ==Structure of ulilysin mutant M290L== |
| - | <StructureSection load='3lum' size='340' side='right' caption='[[3lum]], [[Resolution|resolution]] 1.70Å' scene=''> | + | <StructureSection load='3lum' size='340' side='right'caption='[[3lum]], [[Resolution|resolution]] 1.70Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3lum]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Atcc_35395 Atcc 35395]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3LUM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3LUM FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3lum]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Atcc_35395 Atcc 35395]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3LUM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3LUM FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ARG:ARGININE'>ARG</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=VAL:VALINE'>VAL</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ARG:ARGININE'>ARG</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=VAL:VALINE'>VAL</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3lun|3lun]]</td></tr> | + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3lun|3lun]]</div></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MA_3214 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=2214 ATCC 35395])</td></tr> | + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MA_3214 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=2214 ATCC 35395])</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=3lum FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3lum OCA], [http://pdbe.org/3lum PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3lum RCSB], [http://www.ebi.ac.uk/pdbsum/3lum PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3lum 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=3lum FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3lum OCA], [https://pdbe.org/3lum PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3lum RCSB], [https://www.ebi.ac.uk/pdbsum/3lum PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3lum ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/ULIL_METAC ULIL_METAC]] Metalloprotease which in vitro specifically cleaves IGFBP-2 to -6, insulin, and extracellular matrix proteins but not IGFBP-1 or IGF-II. Shows a preference for substrates with an arginine in the P1' position, the first position downstream of the scissile bond.<ref>PMID:16627477</ref> | + | [[https://www.uniprot.org/uniprot/ULIL_METAC ULIL_METAC]] Metalloprotease which in vitro specifically cleaves IGFBP-2 to -6, insulin, and extracellular matrix proteins but not IGFBP-1 or IGF-II. Shows a preference for substrates with an arginine in the P1' position, the first position downstream of the scissile bond.<ref>PMID:16627477</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Atcc 35395]] | | [[Category: Atcc 35395]] |
| | + | [[Category: Large Structures]] |
| | [[Category: Baumann, U]] | | [[Category: Baumann, U]] |
| | [[Category: Garcia-Castellanos, R]] | | [[Category: Garcia-Castellanos, R]] |
| Structural highlights
Function
[ULIL_METAC] Metalloprotease which in vitro specifically cleaves IGFBP-2 to -6, insulin, and extracellular matrix proteins but not IGFBP-1 or IGF-II. Shows a preference for substrates with an arginine in the P1' position, the first position downstream of the scissile bond.[1]
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
The metzincins are a clan of metallopeptidases consisting of families that share a series of structural elements. Among them is the Met-turn, a tight 1,4-turn found directly below the zinc-binding site, which is structurally and spatially conserved and invariantly shows a methionine at position 3 in all metzincins identified. The reason for this conservation has been a matter of debate since its discovery. We have studied this structural element in Methanosarcina acetivorans ulilysin, the structural prototype of the pappalysin family, by generating 10 mutants that replaced methionine with proteogenic amino acids. We compared recombinant overexpression yields, autolytic and tryptic activation, proteolytic activity, thermal stability, and three-dimensional structure with those of the wild type. All forms were soluble and could be purified, although with varying yields, and three variants underwent autolysis, could be activated by trypsin, and displayed significant proteolytic activity. All variants were analyzed for the thermal stability of their zymogens. None of the mutants analyzed proved more stable or active than the wild type. Both bulky and small side chains, as well as hydrophilic ones, showed diminished thermal stability. Two mutants, leucine and cysteine, crystallized and showed three-dimensional structures that were indistinguishable from the wild type. These studies reveal that the Met-turn acts as a plug that snugly inserts laterally into a core structure created by the protein segment engaged in zinc binding and thus contributes to its structural integrity, which is indispensable for function. Replacement of the methionine with residues that deviate in size, side-chain conformation, and chemical properties impairs the plug-core interaction and prejudices molecular stability and activity.
On the relevance of the Met-turn methionine in metzincins.,Tallant C, Garcia-Castellanos R, Baumann U, Gomis-Ruth FX J Biol Chem. 2010 Apr 30;285(18):13951-7. Epub 2010 Mar 4. PMID:20202937[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Tallant C, Garcia-Castellanos R, Seco J, Baumann U, Gomis-Ruth FX. Molecular analysis of ulilysin, the structural prototype of a new family of metzincin metalloproteases. J Biol Chem. 2006 Jun 30;281(26):17920-8. Epub 2006 Apr 20. PMID:16627477 doi:10.1074/jbc.M600907200
- ↑ Tallant C, Garcia-Castellanos R, Baumann U, Gomis-Ruth FX. On the relevance of the Met-turn methionine in metzincins. J Biol Chem. 2010 Apr 30;285(18):13951-7. Epub 2010 Mar 4. PMID:20202937 doi:10.1074/jbc.M109.083378
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