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| | ==ENGINEERED LIPOCALIN DIGA16 IN COMPLEX WITH DIGOXIGENIN== | | ==ENGINEERED LIPOCALIN DIGA16 IN COMPLEX WITH DIGOXIGENIN== |
| - | <StructureSection load='1lke' size='340' side='right' caption='[[1lke]], [[Resolution|resolution]] 1.90Å' scene=''> | + | <StructureSection load='1lke' size='340' side='right'caption='[[1lke]], [[Resolution|resolution]] 1.90Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1lke]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Large_white_butterfly Large white butterfly]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1LKE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1LKE FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1lke]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Pieris_brassicae Pieris brassicae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1LKE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1LKE FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DOG:DIGOXIGENIN'>DOG</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]] 1.9Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1bbp|1bbp]], [[1n0s|1n0s]], [[1kxo|1kxo]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DOG:DIGOXIGENIN'>DOG</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=1lke FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1lke OCA], [http://pdbe.org/1lke PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1lke RCSB], [http://www.ebi.ac.uk/pdbsum/1lke PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1lke 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=1lke FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1lke OCA], [https://pdbe.org/1lke PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1lke RCSB], [https://www.ebi.ac.uk/pdbsum/1lke PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1lke ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/BBP_PIEBR BBP_PIEBR]] This protein binds the blue pigments bilins.<ref>PMID:3202956</ref> | + | [https://www.uniprot.org/uniprot/BBP_PIEBR BBP_PIEBR] This protein binds the blue pigments bilins.<ref>PMID:3202956</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | <jmolCheckbox> | | <jmolCheckbox> |
| | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/lk/1lke_consurf.spt"</scriptWhenChecked> | | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/lk/1lke_consurf.spt"</scriptWhenChecked> |
| - | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> |
| | <text>to colour the structure by Evolutionary Conservation</text> | | <text>to colour the structure by Evolutionary Conservation</text> |
| | </jmolCheckbox> | | </jmolCheckbox> |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Large white butterfly]] | + | [[Category: Large Structures]] |
| - | [[Category: Korndoerfer, I P]]
| + | |
| - | [[Category: Skerra, A]]
| + | |
| - | [[Category: Anticalin]]
| + | |
| - | [[Category: Digoxigenin]]
| + | |
| - | [[Category: Genetical engineering]]
| + | |
| - | [[Category: Ligand binding protein]]
| + | |
| - | [[Category: Lipocalin]]
| + | |
| | [[Category: Pieris brassicae]] | | [[Category: Pieris brassicae]] |
| | + | [[Category: Korndoerfer IP]] |
| | + | [[Category: Skerra A]] |
| Structural highlights
Function
BBP_PIEBR This protein binds the blue pigments bilins.[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
DigA16 is an artificial digoxigenin-binding protein, which was derived from the bilin-binding protein, a lipocalin of Pieris brassicae, via reshaping of its natural ligand pocket. Here we report the crystal structures of DigA16 in the presence of either digoxigenin or digitoxigenin and for the apo-protein at resolutions below 1.9A. As a consequence of the altogether 17 amino acid substitutions within the binding site significant structural changes have occurred in the four loops that form the entrance to the ligand pocket on top of the structurally conserved beta-barrel framework. For example, one loop adopts a new alpha-helical backbone structure, which seems to be induced by few critical side-chain contacts. Digoxigenin becomes almost fully buried (by 95%) upon complexation, whereby specificity for the hydrophilic steroid is maintained through hydrogen-bonding networks and shape complementarity. The differential binding of the related steroid digitoxigenin is mainly governed by an internal histidine residue, whose side-chain undergoes significant induced fit. Among those amino acids that line the ligand pocket two tyrosine and one tryptophan residue provide the largest contacts. Interestingly, corresponding three side-chains are found with the same mutual orientation in the anti-digoxigenin antibody 26-10, even though the hapten orientation is quite different there and only 66% of the steroid surface is buried in the combining site. Hence, in the case of the engineered lipocalin DigA16 an example of convergent in vitro evolution is observed. Generally, the remarkable structural plasticity of the loop region and the role of polar residues in the binding site illustrate the potential of the lipocalin scaffold for the generation of specific receptor proteins towards a variety of ligands.
Structural mechanism of specific ligand recognition by a lipocalin tailored for the complexation of digoxigenin.,Korndorfer IP, Schlehuber S, Skerra A J Mol Biol. 2003 Jul 4;330(2):385-96. PMID:12823976[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Suter F, Kayser H, Zuber H. The complete amino-acid sequence of the bilin-binding protein from Pieris brassicae and its similarity to a family of serum transport proteins like the retinol-binding proteins. Biol Chem Hoppe Seyler. 1988 Jun;369(6):497-505. PMID:3202956
- ↑ Korndorfer IP, Schlehuber S, Skerra A. Structural mechanism of specific ligand recognition by a lipocalin tailored for the complexation of digoxigenin. J Mol Biol. 2003 Jul 4;330(2):385-96. PMID:12823976
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