|
|
| Line 3: |
Line 3: |
| | <StructureSection load='6saz' size='340' side='right'caption='[[6saz]], [[Resolution|resolution]] 3.00Å' scene=''> | | <StructureSection load='6saz' size='340' side='right'caption='[[6saz]], [[Resolution|resolution]] 3.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6saz]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/ ] and [http://en.wikipedia.org/wiki/Astacus_astacus Astacus astacus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6SAZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6SAZ FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6saz]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Astacus_astacus Astacus astacus] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6SAZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6SAZ FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</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]] 3Å</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='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=6saz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6saz OCA], [http://pdbe.org/6saz PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6saz RCSB], [http://www.ebi.ac.uk/pdbsum/6saz PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6saz 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=6saz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6saz OCA], [https://pdbe.org/6saz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6saz RCSB], [https://www.ebi.ac.uk/pdbsum/6saz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6saz 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_HUMAN FETUB_HUMAN]] 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 (By similarity). | + | [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 == |
| Line 19: |
Line 19: |
| | </div> | | </div> |
| | <div class="pdbe-citations 6saz" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 6saz" 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: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Cuppari, A]] | + | [[Category: Cuppari A]] |
| - | [[Category: Floehr, J]] | + | [[Category: Floehr J]] |
| - | [[Category: Gomis-Ruth, F X]] | + | [[Category: Gomis-Ruth FX]] |
| - | [[Category: Guevara, T]] | + | [[Category: Guevara T]] |
| - | [[Category: Jahnen-Dechent, W]] | + | [[Category: Jahnen-Dechent W]] |
| - | [[Category: Korschgen, H]] | + | [[Category: Korschgen H]] |
| - | [[Category: Kuske, M]] | + | [[Category: Kuske M]] |
| - | [[Category: Schmitz, C]] | + | [[Category: Schmitz C]] |
| - | [[Category: Stocker, W]] | + | [[Category: Stocker W]] |
| - | [[Category: Yiallouros, I]] | + | [[Category: Yiallouros I]] |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Limited proteolysis]]
| + | |
| - | [[Category: Mammalian fertilization]]
| + | |
| - | [[Category: Metallopeptidase]]
| + | |
| - | [[Category: Polyspermy]]
| + | |
| - | [[Category: Protein inhibitor]]
| + | |
| - | [[Category: Sperm-egg fusion]]
| + | |
| 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
Human fetuin-B plays a key physiological role in human fertility through its inhibitory action on ovastacin, a member of the astacin family of metallopeptidases. The inhibitor consists of tandem cystatin-like domains (CY1 and CY2), which are connected by a linker containing a "CPDCP-trunk" and followed by a C-terminal region (CTR) void of regular secondary structure. Here, we solved the crystal structure of the complex of the inhibitor with archetypal astacin from crayfish, which is a useful model of human ovastacin. Two hairpins from CY2, the linker, and the tip of the "legumain-binding loop" of CY1 inhibit crayfish astacin following the "raised-elephant-trunk mechanism" recently reported for mouse fetuin-B. This inhibition is exerted by blocking active-site cleft sub-sites upstream and downstream of the catalytic zinc ion, but not those flanking the scissile bond. However, contrary to the mouse complex, which was obtained with fetuin-B nicked at a single site but otherwise intact, most of the CTR was proteolytically removed during crystallization of the human complex. Moreover, the two complexes present in the crystallographic asymmetric unit diverged in the relative arrangement of CY1 and CY2, while the two complexes found for the mouse complex crystal structure were equivalent. Biochemical studies in vitro confirmed the differential cleavage susceptibility of human and mouse fetuin-B in front of crayfish astacin and revealed that the cleaved human inhibitor blocks crayfish astacin and human meprin alpha and beta only slightly less potently than the intact variant. Therefore, the CTR of animal fetuin-B orthologs may have a function in maintaining a particular relative orientation of CY1 and CY2 that nonetheless is dispensable for peptidase inhibition.
The C-terminal region of human plasma fetuin-B is dispensable for the raised-elephant-trunk mechanism of inhibition of astacin metallopeptidases.,Guevara T, Korschgen H, Cuppari A, Schmitz C, Kuske M, Yiallouros I, Floehr J, Jahnen-Dechent W, Stocker W, Gomis-Ruth FX Sci Rep. 2019 Oct 11;9(1):14683. doi: 10.1038/s41598-019-51095-y. PMID:31604990[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Guevara T, Korschgen H, Cuppari A, Schmitz C, Kuske M, Yiallouros I, Floehr J, Jahnen-Dechent W, Stocker W, Gomis-Ruth FX. The C-terminal region of human plasma fetuin-B is dispensable for the raised-elephant-trunk mechanism of inhibition of astacin metallopeptidases. Sci Rep. 2019 Oct 11;9(1):14683. doi: 10.1038/s41598-019-51095-y. PMID:31604990 doi:http://dx.doi.org/10.1038/s41598-019-51095-y
|
