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| | <StructureSection load='5j7c' size='340' side='right'caption='[[5j7c]], [[Resolution|resolution]] 2.54Å' scene=''> | | <StructureSection load='5j7c' size='340' side='right'caption='[[5j7c]], [[Resolution|resolution]] 2.54Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5j7c]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Gallus_gallus Gallus gallus] and [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5J7C OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5J7C FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5j7c]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Gallus_gallus Gallus gallus] 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=5J7C OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5J7C FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5j7k|5j7k]]</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]] 2.535Å</td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Lysozyme Lysozyme], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.1.17 3.2.1.17] </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=5j7c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5j7c OCA], [https://pdbe.org/5j7c PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5j7c RCSB], [https://www.ebi.ac.uk/pdbsum/5j7c PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5j7c ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5j7c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5j7c OCA], [http://pdbe.org/5j7c PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5j7c RCSB], [http://www.ebi.ac.uk/pdbsum/5j7c PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5j7c ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/LYSC_CHICK LYSC_CHICK]] Lysozymes have primarily a bacteriolytic function; those in tissues and body fluids are associated with the monocyte-macrophage system and enhance the activity of immunoagents. Has bacteriolytic activity against M.luteus.<ref>PMID:22044478</ref> | + | [https://www.uniprot.org/uniprot/LYSC_CHICK LYSC_CHICK] Lysozymes have primarily a bacteriolytic function; those in tissues and body fluids are associated with the monocyte-macrophage system and enhance the activity of immunoagents. Has bacteriolytic activity against M.luteus.<ref>PMID:22044478</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Gallus gallus]] | | [[Category: Gallus gallus]] |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Lysozyme]]
| + | [[Category: Buckle AM]] |
| - | [[Category: Buckle, A M]] | + | [[Category: Drinkwater N]] |
| - | [[Category: Drinkwater, N]] | + | [[Category: McGowan S]] |
| - | [[Category: McGowan, S]] | + | [[Category: Porebski BT]] |
| - | [[Category: Porebski, B T]] | + | |
| - | [[Category: Fibronectin type iii]]
| + | |
| - | [[Category: Fn3]]
| + | |
| - | [[Category: High affinity]]
| + | |
| - | [[Category: Protein binding-hydrolase complex]]
| + | |
| - | [[Category: Yeast surface display]]
| + | |
| Structural highlights
Function
LYSC_CHICK Lysozymes have primarily a bacteriolytic function; those in tissues and body fluids are associated with the monocyte-macrophage system and enhance the activity of immunoagents. Has bacteriolytic activity against M.luteus.[1]
Publication Abstract from PubMed
The favorable biophysical attributes of non-antibody scaffolds make them attractive alternatives to monoclonal antibodies. However, due to the well-known stability-function trade-off, these gains tend to be marginal after functional selection. A notable example is the fibronectin Type III (FN3) domain, FNfn10, which has been previously evolved to bind lysozyme with 1 pM affinity (FNfn10-alpha-lys), but suffers from poor thermodynamic and kinetic stability. To explore this stability-function compromise further, we grafted the lysozyme-binding loops from FNfn10-alpha-lys onto our previously engineered, ultra-stable FN3 scaffold, FN3con The resulting variant (FN3con-alpha-lys) bound lysozyme with a markedly reduced affinity, but retained high levels of thermal stability. The crystal structure of FNfn10-alpha-lys in complex with lysozyme revealed unanticipated interactions at the protein-protein interface involving framework residues of FNfn10-alpha-lys, thus explaining the failure to transfer binding via loop grafting. Utilizing this structural information, we redesigned FN3con-alpha-lys and restored picomolar binding affinity to lysozyme, while maintaining thermodynamic stability (with a thermal melting temperature 2-fold higher than that of FNfn10-alpha-lys). FN3con therefore provides an exceptional window of stability to tolerate deleterious mutations, resulting in a substantial advantage for functional design. This study emphasizes the utility of consensus design for the generation of highly stable scaffolds for downstream protein engineering studies.
Circumventing the stability-function trade-off in an engineered FN3 domain.,Porebski BT, Conroy PJ, Drinkwater N, Schofield P, Vazquez-Lombardi R, Hunter MR, Hoke DE, Christ D, McGowan S, Buckle AM Protein Eng Des Sel. 2016 Aug 29. PMID:27578887[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Maehashi K, Matano M, Irisawa T, Uchino M, Kashiwagi Y, Watanabe T. Molecular characterization of goose- and chicken-type lysozymes in emu (Dromaius novaehollandiae): evidence for extremely low lysozyme levels in emu egg white. Gene. 2012 Jan 15;492(1):244-9. doi: 10.1016/j.gene.2011.10.021. Epub 2011 Oct, 25. PMID:22044478 doi:10.1016/j.gene.2011.10.021
- ↑ Porebski BT, Conroy PJ, Drinkwater N, Schofield P, Vazquez-Lombardi R, Hunter MR, Hoke DE, Christ D, McGowan S, Buckle AM. Circumventing the stability-function trade-off in an engineered FN3 domain. Protein Eng Des Sel. 2016 Aug 29. PMID:27578887 doi:http://dx.doi.org/10.1093/protein/gzw046
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