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| | <StructureSection load='6ht9' size='340' side='right'caption='[[6ht9]], [[Resolution|resolution]] 3.10Å' scene=''> | | <StructureSection load='6ht9' size='340' side='right'caption='[[6ht9]], [[Resolution|resolution]] 3.10Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6ht9]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Astacus_astacus Astacus astacus] and [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6HT9 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6HT9 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6ht9]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Astacus_astacus Astacus astacus] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6HT9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6HT9 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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]] 3.1Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Fetub ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Astacin Astacin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.24.21 3.4.24.21] </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=6ht9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ht9 OCA], [https://pdbe.org/6ht9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6ht9 RCSB], [https://www.ebi.ac.uk/pdbsum/6ht9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6ht9 ProSAT]</span></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=6ht9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ht9 OCA], [http://pdbe.org/6ht9 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ht9 RCSB], [http://www.ebi.ac.uk/pdbsum/6ht9 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ht9 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/ASTA_ASTAS ASTA_ASTAS]] This protease prefers to cleave in front of small aliphatic residues (P1'). The presence of Lys or Arg in the P1 and P2 position yields high-turnover substrates. In the P3 position the enzyme prefers Pro > Val > Leu > Ala > Gly. [[http://www.uniprot.org/uniprot/FETUB_MOUSE FETUB_MOUSE]] Protease inhibitor required for egg fertilization. Required to prevent premature zona pellucida hardening before fertilization, probably by inhibiting the protease activity of ASTL, a protease that mediates the cleavage of ZP2 and triggers zona pellucida hardening.<ref>PMID:23562279</ref> | + | [https://www.uniprot.org/uniprot/ASTA_ASTAS ASTA_ASTAS] This protease prefers to cleave in front of small aliphatic residues (P1'). The presence of Lys or Arg in the P1 and P2 position yields high-turnover substrates. In the P3 position the enzyme prefers Pro > Val > Leu > Ala > Gly. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 6ht9" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 6ht9" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Proteinase 3D structures|Proteinase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Astacin]] | |
| | [[Category: Astacus astacus]] | | [[Category: Astacus astacus]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Mus musculus]] |
| - | [[Category: Cuppari, A]] | + | [[Category: Cuppari A]] |
| - | [[Category: Gomis-Ruth, F X]] | + | [[Category: Gomis-Ruth FX]] |
| - | [[Category: Goulas, T]] | + | [[Category: Goulas T]] |
| - | [[Category: Guevara, T]] | + | [[Category: Guevara T]] |
| - | [[Category: Cystatin]]
| + | |
| - | [[Category: Fetuin]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Metallopeptidase]]
| + | |
| - | [[Category: Ovastacin inhibitor]]
| + | |
| - | [[Category: Peptidase inhibitor]]
| + | |
| Structural highlights
Function
ASTA_ASTAS This protease prefers to cleave in front of small aliphatic residues (P1'). The presence of Lys or Arg in the P1 and P2 position yields high-turnover substrates. In the P3 position the enzyme prefers Pro > Val > Leu > Ala > Gly.
Publication Abstract from PubMed
Mammalian fetuin-A and fetuin-B are abundant serum proteins with pleiotropic functions. Fetuin-B is a highly selective and potent inhibitor of metallo-peptidases (MPs) of the astacin family, which includes ovastacin in mammals. By inhibiting ovastacin, fetuin-B is essential for female fertility. The crystal structure of fetuin-B was determined unbound and in complex with archetypal astacin, and it was found that the inhibitor has tandem cystatin-type modules (CY1 and CY2). They are connected by an exposed linker with a rigid, disulfide-linked 'CPDCP-trunk', and are followed by a C-terminal region (CTR) with little regular secondary structure. The CPDCP-trunk and a hairpin of CY2 form a bipartite wedge, which slots into the active-site cleft of the MP. These elements occupy the nonprimed and primed sides of the cleft, respectively, but spare the specificity pocket so that the inhibitor is not cleaved. The aspartate in the trunk blocks the catalytic zinc of astacin, while the CY2 hairpin binds through a QWVXGP motif. The CY1 module assists in structural integrity and the CTR is not involved in inhibition, as verified by in vitro studies using a cohort of mutants and variants. Overall, the inhibition conforms to a novel 'raised-elephant-trunk' mechanism for MPs, which is reminiscent of single-domain cystatins that target cysteine peptidases. Over 200 sequences from vertebrates have been annotated as fetuin-B, underpinning its ubiquity and physiological relevance; accordingly, sequences with conserved CPDCP- and QWVXGP-derived motifs have been found from mammals to cartilaginous fishes. Thus, the raised-elephant-trunk mechanism is likely to be generally valid for the inhibition of astacins by orthologs of fetuin-B.
Structure of mammalian plasma fetuin-B and its mechanism of selective metallopeptidase inhibition.,Cuppari A, Korschgen H, Fahrenkamp D, Schmitz C, Guevara T, Karmilin K, Kuske M, Olf M, Dietzel E, Yiallouros I, de Sanctis D, Goulas T, Weiskirchen R, Jahnen-Dechent W, Floehr J, Stoecker W, Jovine L, Gomis-Ruth FX IUCrJ. 2019 Feb 28;6(Pt 2):317-330. doi: 10.1107/S2052252519001568. eCollection, 2019 Mar 1. PMID:30867929[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Cuppari A, Korschgen H, Fahrenkamp D, Schmitz C, Guevara T, Karmilin K, Kuske M, Olf M, Dietzel E, Yiallouros I, de Sanctis D, Goulas T, Weiskirchen R, Jahnen-Dechent W, Floehr J, Stoecker W, Jovine L, Gomis-Ruth FX. Structure of mammalian plasma fetuin-B and its mechanism of selective metallopeptidase inhibition. IUCrJ. 2019 Feb 28;6(Pt 2):317-330. doi: 10.1107/S2052252519001568. eCollection, 2019 Mar 1. PMID:30867929 doi:http://dx.doi.org/10.1107/S2052252519001568
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