2g7b
From Proteopedia
|
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
Overview
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 Structure
2G7B is a Single protein structure of sequence from Homo sapiens with NA and AZE as ligands. 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 Mon Nov 12 22:15:57 2007
Categories: Homo sapiens | Single protein | Geiger, J.H. | Vaezeslami, S. | AZE | NA | Beta barrel | Crabpii | Crystallography | High resolution | Protonated schiff base | Retinal | Retinoic acid | Retinoids | Schiff base | X-ray
