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== | ==Crystal Structure of the R132K:R111L:L121E mutant of Cellular Retinoic Acid Binding Protein Type II In Complex With All-Trans-Retinal At 1.18 Angstroms Resolution== | ||
<StructureSection load='2g7b' size='340' side='right'caption='[[2g7b]], [[Resolution|resolution]] 1.18Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[2g7b]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2G7B OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2G7B FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.18Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AZE:ALL-TRANS+AXEROPHTHENE'>AZE</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></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=2g7b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2g7b OCA], [https://pdbe.org/2g7b PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2g7b RCSB], [https://www.ebi.ac.uk/pdbsum/2g7b PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2g7b ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/RABP2_HUMAN RABP2_HUMAN] Transports retinoic acid to the nucleus. Regulates the access of retinoic acid to the nuclear retinoic acid receptors. | |||
== Evolutionary Conservation == | |||
[[Image:Consurf_key_small.gif|200px|right]] | |||
Check<jmol> | |||
<jmolCheckbox> | |||
<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/g7/2g7b_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> | |||
<text>to colour the structure by Evolutionary Conservation</text> | |||
</jmolCheckbox> | |||
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2g7b ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Rational redesign of the binding pocket of Cellular Retinoic Acid Binding Protein II (CRABPII) has provided a mutant that can bind retinal as a protonated Schiff base, mimicking the binding observed in rhodopsin. The reengineering was accomplished through a series of choreographed manipulations to ultimately orient the reactive species (the epsilon-amino group of Lys132 and the carbonyl of retinal) in the proper geometry for imine formation. The guiding principle was to achieve the appropriate Burgi-Dunitz trajectory for the reaction to ensue. Through crystallographic analysis of protein mutants incapable of forming the requisite Schiff base, a highly ordered water molecule was identified as a key culprit in orienting retinal in a nonconstructive manner. Removal of the ordered water, along with placing reinforcing mutations to favor the desired orientation of retinal, led to a triple mutant CRABPII protein capable of nanomolar binding of retinal as a protonated Schiff base. The high-resolution crystal structure of all-trans-retinal bound to the CRABPII triple mutant (1.2 A resolution) unequivocally illustrates the imine formed between retinal and the protein. | Rational redesign of the binding pocket of Cellular Retinoic Acid Binding Protein II (CRABPII) has provided a mutant that can bind retinal as a protonated Schiff base, mimicking the binding observed in rhodopsin. The reengineering was accomplished through a series of choreographed manipulations to ultimately orient the reactive species (the epsilon-amino group of Lys132 and the carbonyl of retinal) in the proper geometry for imine formation. The guiding principle was to achieve the appropriate Burgi-Dunitz trajectory for the reaction to ensue. Through crystallographic analysis of protein mutants incapable of forming the requisite Schiff base, a highly ordered water molecule was identified as a key culprit in orienting retinal in a nonconstructive manner. Removal of the ordered water, along with placing reinforcing mutations to favor the desired orientation of retinal, led to a triple mutant CRABPII protein capable of nanomolar binding of retinal as a protonated Schiff base. The high-resolution crystal structure of all-trans-retinal bound to the CRABPII triple mutant (1.2 A resolution) unequivocally illustrates the imine formed between retinal and the protein. | ||
Protein design: reengineering cellular retinoic acid binding protein II into a rhodopsin protein mimic.,Vasileiou C, Vaezeslami S, Crist RM, Rabago-Smith M, Geiger JH, Borhan B J Am Chem Soc. 2007 May 16;129(19):6140-8. Epub 2007 Apr 21. PMID:17447762<ref>PMID:17447762</ref> | |||
== | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
Protein | </div> | ||
<div class="pdbe-citations 2g7b" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[CRABP I ( Cellular Retinoic Acid Binding Protein )|CRABP I ( Cellular Retinoic Acid Binding Protein )]] | |||
*[[Cellular retinoic acid-binding protein 3D structures|Cellular retinoic acid-binding protein 3D structures]] | |||
*[[Gustavo Elberto Epalza Sanchez/Sandbox 1|Gustavo Elberto Epalza Sanchez/Sandbox 1]] | |||
*[[Molecular Playground/CRABP I (Cellular Retinoic Acid Binding Protein)|Molecular Playground/CRABP I (Cellular Retinoic Acid Binding Protein)]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: Geiger | [[Category: Geiger JH]] | ||
[[Category: Vaezeslami | [[Category: Vaezeslami S]] | ||
Latest revision as of 08:13, 17 October 2024
Crystal Structure of the R132K:R111L:L121E mutant of Cellular Retinoic Acid Binding Protein Type II In Complex With All-Trans-Retinal At 1.18 Angstroms ResolutionCrystal Structure of the R132K:R111L:L121E mutant of Cellular Retinoic Acid Binding Protein Type II In Complex With All-Trans-Retinal At 1.18 Angstroms Resolution
Structural highlights
FunctionRABP2_HUMAN Transports retinoic acid to the nucleus. Regulates the access of retinoic acid to the nuclear retinoic acid receptors. 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 PubMedRational redesign of the binding pocket of Cellular Retinoic Acid Binding Protein II (CRABPII) has provided a mutant that can bind retinal as a protonated Schiff base, mimicking the binding observed in rhodopsin. The reengineering was accomplished through a series of choreographed manipulations to ultimately orient the reactive species (the epsilon-amino group of Lys132 and the carbonyl of retinal) in the proper geometry for imine formation. The guiding principle was to achieve the appropriate Burgi-Dunitz trajectory for the reaction to ensue. Through crystallographic analysis of protein mutants incapable of forming the requisite Schiff base, a highly ordered water molecule was identified as a key culprit in orienting retinal in a nonconstructive manner. Removal of the ordered water, along with placing reinforcing mutations to favor the desired orientation of retinal, led to a triple mutant CRABPII protein capable of nanomolar binding of retinal as a protonated Schiff base. The high-resolution crystal structure of all-trans-retinal bound to the CRABPII triple mutant (1.2 A resolution) unequivocally illustrates the imine formed between retinal and the protein. Protein design: reengineering cellular retinoic acid binding protein II into a rhodopsin protein mimic.,Vasileiou C, Vaezeslami S, Crist RM, Rabago-Smith M, Geiger JH, Borhan B J Am Chem Soc. 2007 May 16;129(19):6140-8. Epub 2007 Apr 21. PMID:17447762[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also
References
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