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2g78

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{{STRUCTURE_2g78| PDB=2g78 | SCENE= }}
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'''Crystal Structure of the R132K:Y134F Mutant of Cellular Retinoic Acid Binding Protein Type II in Complex with All-Trans-Retinoic Acid at 1.70 Angstroms Resolution'''
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===Crystal Structure of the R132K:Y134F Mutant of Cellular Retinoic Acid Binding Protein Type II in Complex with All-Trans-Retinoic Acid at 1.70 Angstroms Resolution===
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==Overview==
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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.
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(as it appears on PubMed at http://www.pubmed.gov), where 17447762 is the PubMed ID number.
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{{ABSTRACT_PUBMED_17447762}}
==About this Structure==
==About this Structure==
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[[Category: Retinoid]]
[[Category: Retinoid]]
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Revision as of 10:40, 27 July 2008

Image:2g78.png

Template:STRUCTURE 2g78

Crystal Structure of the R132K:Y134F Mutant of Cellular Retinoic Acid Binding Protein Type II in Complex with All-Trans-Retinoic Acid at 1.70 Angstroms Resolution

Template:ABSTRACT PUBMED 17447762

About this Structure

2G78 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

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 Jul 27 13:40:21 2008

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