4iax: Difference between revisions

← Older edit Newer edit →

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

@@ Line 1: / Line 1: @@
-{{STRUCTURE_4iax|  PDB=4iax  |  SCENE=  }}
+==Engineered human lipocalin 2 (CL31) in complex with Y-DTPA==
-===Engineered human lipocalin 2 (CL31) in complex with Y-DTPA===
+<StructureSection load='4iax' size='340' side='right' caption='[[4iax]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
-{{ABSTRACT_PUBMED_23542582}}
+== Structural highlights ==
+<table><tr><td colspan='2'>[[4iax]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4IAX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4IAX FirstGlance]. <br>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=LIZ:N-{(1S,2S)-2-[BIS(CARBOXYMETHYL)AMINO]CYCLOHEXYL}-N-{(2R)-2-[BIS(CARBOXYMETHYL)AMINO]-3-[4-({[2-HYDROXY-1,1-BIS(HYDROXYMETHYL)ETHYL]CARBAMOTHIOYL}AMINO)PHENYL]PROPYL}GLYCINE'>LIZ</scene>, <scene name='pdbligand=YT3:YTTRIUM+(III)+ION'>YT3</scene></td></tr>
+<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3dsz|3dsz]], [[3dtq|3dtq]], [[4iaw|4iaw]]</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">HNL, LCN2, NGAL ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=4iax FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4iax OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4iax RCSB], [http://www.ebi.ac.uk/pdbsum/4iax PDBsum]</span></td></tr>
+</table>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Modern strategies in radio-immuno therapy and in vivo imaging require robust, small, and specific ligand-binding proteins. In this context we have previously developed artificial lipocalins, so-called Anticalins, with high binding activity toward rare-earth metal-chelate complexes using combinatorial protein design. Here we describe further improvement of the Anticalin C26 via in vitro affinity maturation to yield CL31, which has a fourfold slower dissociation half-life above 2h. Also, we present the crystallographic analyses of both the initial and the improved Anticalin, providing insight into the molecular mechanism of chelated metal binding and the role of amino acid substitutions during the step-wise affinity maturation. Notably, one of the four structurally variable loops that form the ligand pocket in the lipocalin scaffold undergoes a significant conformational change from C26 to CL31, acting as a lid that closes over the accommodated metal-chelate ligand. A systematic mutational study indicated that further improvement of ligand affinity is difficult to achieve while providing clues on the contribution of relevant side chains in the engineered binding pocket. Unexpectedly, some of the amino acid replacements led to strong increases - more then 10-fold - in the yield of soluble protein from periplasmic secretion in Escherichia coli.
-==Function==
+Structure-guided engineering of Anticalins with improved binding behavior and biochemical characteristics for application in radio-immuno imaging and/or therapy.,Eggenstein E, Eichinger A, Kim HJ, Skerra A J Struct Biol. 2013 Mar 27. pii: S1047-8477(13)00080-4. doi:, 10.1016/j.jsb.2013.03.009. PMID:23542582<ref>PMID:23542582</ref>
-[[http://www.uniprot.org/uniprot/NGAL_HUMAN NGAL_HUMAN]] Iron-trafficking protein involved in multiple processes such as apoptosis, innate immunity and renal development. Binds iron through association with 2,5-dihydroxybenzoic acid (2,5-DHBA), a siderophore that shares structural similarities with bacterial enterobactin, and delivers or removes iron from the cell, depending on the context. Iron-bound form (holo-24p3) is internalized following binding to the SLC22A17 (24p3R) receptor, leading to release of iron and subsequent increase of intracellular iron concentration. In contrast, association of the iron-free form (apo-24p3) with the SLC22A17 (24p3R) receptor is followed by association with an intracellular siderophore, iron chelation and iron transfer to the extracellular medium, thereby reducing intracellular iron concentration. Involved in apoptosis due to interleukin-3 (IL3) deprivation: iron-loaded form increases intracellular iron concentration without promoting apoptosis, while iron-free form decreases intracellular iron levels, inducing expression of the proapoptotic protein BCL2L11/BIM, resulting in apoptosis. Involved in innate immunity, possibly by sequestrating iron, leading to limit bacterial growth.<ref>PMID:12453413</ref>
-==About this Structure==
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[4iax]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4IAX OCA].
+</div>
-==Reference==
+==See Also==
-<ref group="xtra">PMID:023542582</ref><references group="xtra"/><references/>
+*[[Neutrophil gelatinase-associated lipocalin|Neutrophil gelatinase-associated lipocalin]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
 [[Category: Human]]
-[[Category: Eichinger, A.]]
+[[Category: Eichinger, A]]
-[[Category: Skerra, A.]]
+[[Category: Skerra, A]]
 [[Category: Beta-barrel]]
 [[Category: Binding protein]]