2g79: Difference between revisions

Revision as of 04:46, 4 May 2008

Crystal Structure of the R132K:Y134F Mutant of Cellular Retinoic Acid Binding Protein Type II in Complex with All-Trans-Retinal at 1.69 Angstroms Resolution

OverviewOverview

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.

About this StructureAbout this Structure

2G79 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

ReferenceReference

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 Page seeded by OCA on Sun May 4 04:46:06 2008

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OCA

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 [[Image:2g79.gif|left|200px]]
- {{Structure
+<!--
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-|LIGAND= <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=RET:RETINAL'>RET</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>
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-|GENE= CRABP2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
+-->
-|DOMAIN=
+{{STRUCTURE_2g79|  PDB=2g79  |  SCENE=  }}
-|RELATEDENTRY=[[2g78|2G78]], [[2g7a|2G7A]], [[2g7b|2G7B]]
-|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2g79 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2g79 OCA], [http://www.ebi.ac.uk/pdbsum/2g79 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2g79 RCSB]</span>
-}}
 '''Crystal Structure of the R132K:Y134F Mutant of Cellular Retinoic Acid Binding Protein Type II in Complex with All-Trans-Retinal at 1.69 Angstroms Resolution'''
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 [[Category: Geiger, J H.]]
 [[Category: Vaezeslami, S.]]
-[[Category: beta barrel]]
+[[Category: Beta barrel]]
-[[Category: crabpii]]
+[[Category: Crabpii]]
-[[Category: crystallography]]
+[[Category: Crystallography]]
-[[Category: high resolution]]
+[[Category: High resolution]]
-[[Category: retinal]]
+[[Category: Retinal]]
-[[Category: retinoic acid]]
+[[Category: Retinoic acid]]
-[[Category: retinoid]]
+[[Category: Retinoid]]
-[[Category: x-ray]]
+[[Category: X-ray]]
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May  4 04:46:06 2008''
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 03:12:47 2008''