Protein phosphorylation and dephosphorylation are essential to all aspects of biology. Protein phosphatase 2A(PP2A) is an important serine/threonine phosphatase that plays a critical role in cellular physiology includ...
Protein phosphorylation and dephosphorylation are essential to all aspects of biology. Protein phosphatase 2A(PP2A) is an important serine/threonine phosphatase that plays a critical role in cellular physiology including cell cycle,cell proliferation,development,and regulation of multiple signal transduction ***2A is also an important tumor suppressor *** PP2A core enzyme comprises a 65-kD scaffold subunit(known as A or PR65 subunit) and a 36-kD catalytic subunit(or C subunit).To gain full activity towards specific substrates,the PP2A core enzyme interacts with a variable regulatory subunit to form a heterotrimeric *** variable regulatory subunits consist of 4 families,with at least 16 different *** this regard,the regulatory subunits determine the substrate specificity as well as the spatial and temporal functions of ***2A interacts with a large number of regulatory proteins and is subject to two primary forms of regulation:methylation and *** this presentation,I will discuss structural insights into the function of PP2A by focusing on several recent structures:the core enzyme,two holoenzyme complexes, the core enzyme bound to a PP2A-specific methyl esterase,and the phosphotyrosyl phosphatase activator(PTPA).An emphasis is given to the underlying mechanisms of PP2A function.
＜正＞β-catenin is a key component of the canonical Wnt signaling ***-interacting protein-1（TIP-1） is an atypical scaffolding protein containing one PDZ domain only and able to bind c-terminalβ-catenin with high a...
＜正＞β-catenin is a key component of the canonical Wnt signaling ***-interacting protein-1（TIP-1） is an atypical scaffolding protein containing one PDZ domain only and able to bind c-terminalβ-catenin with high affinity and thus inhibit its transcriptional *** resolution crystal structures of c-terminalβ-catenin bound TIP-1 complex,TIP-1 wild type and c-terminal truncated TIP-1 have been *** comparison of peptide-free and peptide-bound TIP-1 reveals that drastic conformational changes of loopβB-βC region are required to avoid heavy conflict with incoming c-terminalβ-catenin,which is in sharp contrast with other published structures of PDZ domains where free form conformation is ready to take *** addition to the last four amino acids ofβ-catenin bound to canonical peptide binding pocket of PDZ domain,loopβB-βC region of TIP-1 forms an additional binding cavity to anchor more amino acids through a hydrophobic residue pair of Trp776 and *** presumably is the cause of much higher affinity of c-terminalβ-catenin binding to TIP-1 than other PDZ *** of a conserved amino acid Pro45 to alanine or serine and Trp776 to alanine leads to about 15-fold and 80-fold decreased binding affinity measured by isothermal titration calorimetry experiments,*** results provide first molecular details of c-terminalβ-catenin recognition by TIP-1 protein.
Endo-β-N-acetylglycosaminidases（ENGases） belonging to the GH85 families of glycoside hydrolases are dual specificity enzymes with an ability to catalyze hydrolysis and transglycosylation *** and transglycosylation ...
详细信息
Endo-β-N-acetylglycosaminidases（ENGases） belonging to the GH85 families of glycoside hydrolases are dual specificity enzymes with an ability to catalyze hydrolysis and transglycosylation *** and transglycosylation are achieved via a unique substrate assisted ***,these enzymes have been the focus of intense research because of their potential for synthesis of novel,regio-and sterio-specific glycopeptides and *** of the 3D structure has severely hampered the rational engineering of these enzymes. We have determined the three dimensional structure of ENGase from Arthrobacter protophormiae（Endo-A） in complex with GlcNAc-thiazoline and ***-A is composed of three domains-a classic（β/α） TIM-barrel domain found in several GH18 family ENGases,a Carbohydrate Binding Module（CBM） and an Fn3 domain,which have never been reported before for *** carbohydrate moiety sits in a cleft region surrounded by aromatic residues just above the *** conserved essential catalytic residues-E173,N171 and Y205 are within hydrogen bonding distance of the substrate.W216 and W244 regulate access to the active site during transglycosylation by serving as "gate-keepers".Residues N241,F243 and Y299 play a role in transglycosylation due to their proximity to ***,Y299F mutation resulted in a 3 fold increase in the transglycosylation *** structure provides insights into the catalytic mechanism at molecular level and could assist rational engineering of ENGases.
暂无评论