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| [[Image:2g78.gif|left|200px]] | | {{Seed}} |
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| {{STRUCTURE_2g78| PDB=2g78 | SCENE= }} | | {{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'''
| | ===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.
| | The line below this paragraph, {{ABSTRACT_PUBMED_17447762}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 17447762 is the PubMed ID number. |
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| | {{ABSTRACT_PUBMED_17447762}} |
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| ==About this Structure== | | ==About this Structure== |
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| [[Category: Retinoid]] | | [[Category: Retinoid]] |
| [[Category: X-ray]] | | [[Category: X-ray]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 04:46:07 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Jul 27 13:40:21 2008'' |