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{{STRUCTURE_2g7b| PDB=2g7b | SCENE= }} | |||
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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''' | '''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''' | ||
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[[Category: Geiger, J H.]] | [[Category: Geiger, J H.]] | ||
[[Category: Vaezeslami, S.]] | [[Category: Vaezeslami, S.]] | ||
[[Category: | [[Category: Beta barrel]] | ||
[[Category: | [[Category: Crabpii]] | ||
[[Category: | [[Category: Crystallography]] | ||
[[Category: | [[Category: High resolution]] | ||
[[Category: | [[Category: Protonated schiff base]] | ||
[[Category: | [[Category: Retinal]] | ||
[[Category: | [[Category: Retinoic acid]] | ||
[[Category: | [[Category: Retinoid]] | ||
[[Category: | [[Category: Schiff base]] | ||
[[Category: | [[Category: X-ray]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 04:46:20 2008'' | |||
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Revision as of 04:46, 4 May 2008
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
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
2G7B 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 04:46:20 2008