scholarly journals Kinetics and Optimization of the Lysine–Isopeptide Bond Forming Sortase Enzyme from Corynebacterium diphtheriae

2020 ◽  
Vol 31 (6) ◽  
pp. 1624-1634
Author(s):  
Christopher K. Sue ◽  
Scott A. McConnell ◽  
Ken Ellis-Guardiola ◽  
John M. Muroski ◽  
Rachel A. McAllister ◽  
...  
Keyword(s):  
Corynebacterium Diphtheriae ◽  
Bond Forming ◽  
Isopeptide Bond

scholarly journals Sortase-assembled pili in Corynebacterium diphtheriae are built using a latch mechanism

2021 ◽  
Vol 118 (12) ◽  
pp. e2019649118
Author(s):  
Scott A. McConnell ◽  
Rachel A. McAllister ◽  
Brendan R. Amer ◽  
Brendan J. Mahoney ◽  
Christopher K. Sue ◽  
...  
Keyword(s):  
Solution Structure ◽  
Corynebacterium Diphtheriae ◽  
Crosslinking Reaction ◽  
Gram Positive ◽  
Kinetic Measurements ◽  
Sorting Signal ◽  
Gram Positive Bacteria ◽  
Isopeptide Bond ◽  
Assembly Mechanism ◽  
Binding Groove

Gram-positive bacteria assemble pili (fimbriae) on their surfaces to adhere to host tissues and to promote polymicrobial interactions. These hair-like structures, although very thin (1 to 5 nm), exhibit impressive tensile strengths because their protein components (pilins) are covalently crosslinked together via lysine–isopeptide bonds by pilus-specific sortase enzymes. While atomic structures of isolated pilins have been determined, how they are joined together by sortases and how these interpilin crosslinks stabilize pilus structure are poorly understood. Using a reconstituted pilus assembly system and hybrid structural biology methods, we elucidated the solution structure and dynamics of the crosslinked interface that is repeated to build the prototypical SpaA pilus from Corynebacterium diphtheriae. We show that sortase-catalyzed introduction of a K190-T494 isopeptide bond between adjacent SpaA pilins causes them to form a rigid interface in which the LPLTG sorting signal is inserted into a large binding groove. Cellular and quantitative kinetic measurements of the crosslinking reaction shed light onto the mechanism of pilus biogenesis. We propose that the pilus-specific sortase in C. diphtheriae uses a latch mechanism to select K190 on SpaA for crosslinking in which the sorting signal is partially transferred from the enzyme to a binding groove in SpaA in order to facilitate catalysis. This process is facilitated by a conserved loop in SpaA, which after crosslinking forms a stabilizing latch that covers the K190-T494 isopeptide bond. General features of the structure and sortase-catalyzed assembly mechanism of the SpaA pilus are likely conserved in Gram-positive bacteria.

scholarly journals Protein Labeling via a Specific Lysine-Isopeptide Bond Using the Pilin Polymerizing Sortase from Corynebacterium diphtheriae

2018 ◽  
Vol 140 (27) ◽  
pp. 8420-8423 ◽  
Author(s):  
Scott A. McConnell ◽  
Brendan R. Amer ◽  
John Muroski ◽  
Janine Fu ◽  
Chungyu Chang ◽  
...  
Keyword(s):  
Corynebacterium Diphtheriae ◽  
Protein Labeling ◽  
Isopeptide Bond

Five‐Step Synthesis of Yaequinolones J1 and J2

2019 ◽  
Author(s):  
Johannes Schwan ◽  
Merlin Kleoff ◽  
Philipp Heretsch ◽  
Mathias Christmann
Keyword(s):  
Bond Forming ◽  
Aldol Cyclization

A concise synthesis of yaequinolones J1 and J2 is reported. The route is based on the aryne insertion into the σ- C–N-bond of an unsymmetric imide followed by a diastereoselective aldol cyclization of the resulting N-acylated aminobenzophenone. The chromene motif is generated in the first step by an organocatalytic tandem Knoevenagel-electrocyclization of citral and 2-bromoresorcinol. The approach adheres to the ideality-principle, using almost exclusively strategic bond-forming<br>reactions.

Radical Capture at Ni(II) Complexes: C-C, C-N, and C-O Bond Formation

2019 ◽  
Author(s):  
Abolghasem (Gus) Bakhoda ◽  
Stefan Wiese ◽  
Christine Greene ◽  
Bryan C. Figula ◽  
Jeffery A. Bertke ◽  
...  
Keyword(s):  
Functional Groups ◽  
Bond Formation ◽  
Dft Studies ◽  
Bond Forming ◽  
Aryl Amines ◽  
Shed Light ◽  
Competing Pathways

<p>The dinuclear b-diketiminato Ni<sup>II</sup><i>tert</i>-butoxide {[Me<sub>3</sub>NN]Ni}<sub>2</sub>(<i>μ</i>-O<i><sup>t</sup></i>Bu)<sub>2 </sub>(<b>2</b>), synthesized from [Me<sub>3</sub>NN]Ni(2,4-lutidine) (<b>1</b>) and di-<i>tert</i>-butylperoxide, is a versatile precursor for the synthesis of a series of Ni<sup>II</sup>complexes [Me<sub>3</sub>NN]Ni-FG to illustrate C-C, C-N, and C-O bond formation at Ni<sup>II </sup>via radicals. {[Me<sub>3</sub>NN]Ni}<sub>2</sub>(<i>μ</i>-O<i><sup>t</sup></i>Bu)<sub>2 </sub>reacts with nitromethane, alkyl and aryl amines, acetophenone, benzamide, ammonia and phenols to deliver corresponding mono- or dinuclear [Me<sub>3</sub>NN]Ni-FG species (FG = O<sub>2</sub>NCH<sub>2</sub>, R-NH, ArNH, PhC(O)NH, PhC(O)CH<sub>2</sub>, NH<sub>2</sub>and OAr). Many of these Ni<sup>II </sup>complexes are capable of capturing the benzylic radical PhCH(•)CH<sub>3 </sub>to deliver corresponding PhCH(FG)CH<sub>3 </sub>products featuring C-C, C-N or C-O bonds. DFT studies shed light on the mechanism of these transformations and suggest two competing pathways that depend on the nature of the functional groups. These radical capture reactions at [Ni<sup>II</sup>]-FG complexes outline key C-C, C-N, and C-O bond forming steps and suggest new families of nickel radical relay catalysts.</p>

Bimetallic Radical Redox-Relay Catalysis for the Isomerization of Epoxides to Allylic Alcohols

2019 ◽  
Author(s):  
Ke-Yin Ye ◽  
Terry McCallum ◽  
Song Lin
Keyword(s):  
Ring Opening ◽  
High Reactivity ◽  
Hydrogen Atom Transfer ◽  
Organic Radicals ◽  
Epoxide Ring ◽  
Allylic Alcohols ◽  
Epoxide Ring Opening ◽  
Bond Forming ◽  
Co Catalysts ◽  
The Rich

Organic radicals are generally short-lived intermediates with exceptionally high reactivity. Strategically, achieving synthetically useful transformations mediated by organic radicals requires both efficient initiation and selective termination events. Here, we report a new catalytic strategy, namely bimetallic radical redox-relay, in the regio- and stereoselective rearrangement of epoxides to allylic alcohols. This approach exploits the rich redox chemistry of Ti and Co complexes and merges reductive epoxide ring opening (initiation) with hydrogen atom transfer (termination). Critically, upon effecting key bond-forming and -breaking events, Ti and Co catalysts undergo proton-transfer/electron-transfer with one another to achieve turnover, thus constituting a truly synergistic dual catalytic system.<br>

Visible-Light Photosensitized Aryl and Alkyl Decarboxylative Carbon-Heteroatom and Carbon-Carbon Bond Formations

2019 ◽  
Author(s):  
Tuhin Patra ◽  
Satobhisha Mukherjee ◽  
Jiajia Ma ◽  
Felix Strieth-Kalthoff ◽  
Frank Glorius
Keyword(s):  
Energy Transfer ◽  
Visible Light ◽  
Alkyl Radical ◽  
General Strategy ◽  
Alkyl Radicals ◽  
Bond Forming ◽  
Radical Trapping ◽  
Carbon Carbon Bond ◽  
Radical Generation ◽  
Trapping Agent

<sub>A general strategy to access both aryl and alkyl radicals by photosensitized decarboxylation of the corresponding carboxylic acids esters has been developed. An energy transfer mediated homolysis of unsymmetrical sigma-bonds for a concerted fragmentation/decarboxylation process is involved. As a result, an independent aryl/alkyl radical generation step enables a series of key C-X and C-C bond forming reactions by simply changing the radical trapping agent.</sub>

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