Structural highlights
Function[RABP2_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
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