Redox Regulation of Methionine Aminopeptidase 2 Activity

Abstract

Background:The N-terminal methionine in new eukaryote proteins is removed by methionine aminopeptidases, but how these enzymes are regulated is not known. Results: Methionine aminopeptidase 2 contains a single disulfide bond that exists in oxidized and reduced states and influences enzyme function. Conclusion: MetAP2 is regulated by an allosteric disulfide bond. Significance: This has implications for MetAP2 substrate proteins and other similar enzymes.

Group VII Ethylene Response Factors in Arabidopsis: Regulation and Physiological Roles

“…Thus, even prior to Cys2 modification, regulation of the N-terminal Met cleavage could represent a general mechanism affecting MC-protein stability. Human MetAP2 activity responds to the cytosolic redox state through the thioredoxindependent conversion of a Cys 228 -Cys 448 disulfide bond (Chiu et al, 2014). Such evidence provides a potential link between cellular ROS content and, ultimately, the availability of MC proteins for N-end rule pathwaymediated degradation.…”

Autoregulation of von Willebrand factor function by a disulfide bond switch

“…Peptides were eluted from the slices with 5% formic acid and 50% acetonitrile. Liquid chromatography, mass spectrometry, and data analysis were performed as previously described ( 36 , 37 ). Two peptides encompassing the Cys 1669 -Cys 1670 disulfide bond cysteines (LVLQR CC SGE and TLPREAPDLVLQR CC SGE) were resolved and quantified.…”

Identification of allosteric disulfides from labile bonds in X-ray structures

“…Five known allosteric disulfides were among the 511 labile bonds, which is a validation of this approach for identifying functional disulfides. These are the –RHstaple bonds in methionine aminopeptidase 2 [ 23 ], botulinum neurotoxins [ 24 ] and transglutaminase 2 [ 25 ], the –/+RHhook disulfides in plasminogen [ 26 ] and Lon protease [ 27 ] and the –LHhook bonds in DNA repair protein XRCC1 [ 28 ] and plasminogen [ 26 ] (electronic supplementary material, table S3).…”