No abstract

The single-site catalyst (SSC) characteristic of atomically dispersed active centers will not only maximize the catalytic activity,but also provideapromising platform for establishing the structure-activity relationship.H owever,a rbitrary arrangements of active sites in the existed SSCs make it difficult for mechanism understanding and performance optimization. Now, aw ell-defined ultrathin SSC is fabricated by assembly of metal-porphyrin molecules,w hiche nables the precise identification of the active sites for d-orbital energy engineering.The activity of as-assembled products for electrocatalytic CO 2 reduction is significantly promoted via lifting up the energy level of metal d z 2 orbitals,e xhibiting ar emarkable Faradaic efficiency of 96 %a tt he overpotential of 500 mV. Furthermore,aturnover frequency of 4.21 s À1 is achieved with negligible decayo ver4 8h.Supportinginformation and the ORCID identification number(s) for the author(s) of this article can be found under: https://doi.Figure 5. DFT calculation of electrocatalytic CO 2 reduction on STPyP-Co.A)Calculated free-energys tates of CO 2 reduction to CO on STPyP-Co and MTPyP-Co. B) Optimized geometry of intermediate [STPyP-Co-COOH].C ),D) Spatial representationo fHOMO orbital of [STPyP-Co-COOH] and [MTPyP-Co-COOH] intermediates, respectively.

SMAD6 is a crucial feedback inhibitory regulator of bone morphogenetic protein (BMP)/SMAD signalling. Although little is known regarding the post-transcriptional modification of inhibitory SMADs and the mechanism by which their function is regulated. In this study, using a whole proteomic interaction screen for SMAD6, we identified a large putative E2 ubiquitin-conjugating enzyme UBE2O (E2-230K) as a novel interacting protein of SMAD6. We showed that UBE2O functions as an E2-E3 hybrid to monoubiquitinate SMAD6 at lysine 174 and that the cysteine 885 residue of human UBE2O is necessary for SMAD6 monoubiquitination. Inactivation of the SMAD6 monoubiquitination site specially potentiates the inhibitory ability of SMAD6 against BMP7-induced SMAD1 phosphorylation and transcriptional responses. We also found that UBE2O potentiated BMP7 signalling in a SMAD6-dependent manner. Addressing the molecular mechanism by which UBE2O and monoubiquitinated SMAD6 potentiate BMP7 signalling, we demonstrated that monoubiquitinated SMAD6 impairs the binding affinity of non-modified SMAD6 to the BMP type I receptor. Moreover, UBE2O and SMAD6 cooperated in the regulation of BMP7-induced adipogenesis.