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Structure of a cyclophilin from Citrus sinensis (CsCyp) in complex with cyclosporin AStructure of a cyclophilin from Citrus sinensis (CsCyp) in complex with cyclosporin A
Structural highlights
FunctionD0ELH5_CITSI PPIases accelerate the folding of proteins. It catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides.[RuleBase:RU004223] Publication Abstract from PubMedThe Citrus sinensis cyclophilin CsCyp is a target of the Xanthomonas citri TAL effector PthA, required to elicit cankers on citrus. CsCyp binds the citrus thioredoxin CsTdx and C-terminal domain of RNA Polymerase II (CTD), and is a divergent cyclophilin that carries the additional loop KSGKPLH, invariable cysteines C40 and C168, and conserved glutamate E83. Despite the suggested roles in ATP and metal binding, the function of these unique structural elements remains unknown. Here we show that the conserved cysteines form a disulfide bond that inactivates the enzyme, whereas E83, which belongs to the catalytic loop and is also critical for enzyme activity, is anchored to the divergent loop to maintain the active site open. In addition, we demonstrate that C40 and C168 are required for the interaction with CsTdx and that CsCyp binds the citrus CTD YSPSAP repeat. Our data support the model where formation of the C40-C168 disulfide bond induces a conformational change that disrupts the interaction of the divergent and catalytic loops, via E83, causing the active site to close. This suggests a new type of allosteric regulation in divergent cyclophilins, involving disulfide bond formation and a loop displacement mechanism. A Redox 2-Cys Mechanism Regulates the Catalytic Activity of Divergent Cyclophilins.,Campos BM, Sforca ML, Ambrosio AL, Domingues MN, Souza TA, Barbosa JA, Leme AF, Perez CA, Whittaker SB, Murakami MT, Zeri AC, Benedetti CE Plant Physiol. 2013 May 24. PMID:23709667[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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