scholarly journals Active-Site Controlled, Jahn–Teller Enabled Regioselectivity in Reductive S–C Bond Cleavage of S-Adenosylmethionine in Radical SAM Enzymes

2020 ◽  
Author(s):  
Stella Impano ◽  
Hao Yang ◽  
Richard J. Jodts ◽  
Adrien Pagnier ◽  
Ryan Swimley ◽  
...  
Keyword(s):  
Active Site ◽  
Bond Cleavage ◽  
Radical Sam ◽  
Radical Sam Enzymes ◽  
Jahn Teller

scholarly journals Serine protease dynamics revealed by NMR analysis of the thrombin-thrombomodulin complex

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Riley B. Peacock ◽  
Taylor McGrann ◽  
Marco Tonelli ◽  
Elizabeth A. Komives
Keyword(s):  
Active Site ◽  
Serine Proteases ◽  
Protein C ◽  
Catalytic Mechanism ◽  
Bond Cleavage ◽  
Peptide Bond ◽  
Peptide Bond Cleavage ◽  
Exchange Mass Spectrometry ◽  
Catalytically Active ◽  
Hydrogen Deuterium

AbstractSerine proteases catalyze a multi-step covalent catalytic mechanism of peptide bond cleavage. It has long been assumed that serine proteases including thrombin carry-out catalysis without significant conformational rearrangement of their stable two-β-barrel structure. We present nuclear magnetic resonance (NMR) and hydrogen deuterium exchange mass spectrometry (HDX-MS) experiments on the thrombin-thrombomodulin (TM) complex. Thrombin promotes procoagulative fibrinogen cleavage when fibrinogen engages both the anion binding exosite 1 (ABE1) and the active site. It is thought that TM promotes cleavage of protein C by engaging ABE1 in a similar manner as fibrinogen. Thus, the thrombin-TM complex may represent the catalytically active, ABE1-engaged thrombin. Compared to apo- and active site inhibited-thrombin, we show that thrombin-TM has reduced μs-ms dynamics in the substrate binding (S1) pocket consistent with its known acceleration of protein C binding. Thrombin-TM has increased μs-ms dynamics in a β-strand connecting the TM binding site to the catalytic aspartate. Finally, thrombin-TM had doublet peaks indicative of dynamics that are slow on the NMR timescale in residues along the interface between the two β-barrels. Such dynamics may be responsible for facilitating the N-terminal product release and water molecule entry that are required for hydrolysis of the acyl-enzyme intermediate.

scholarly journals RlmN and Cfr are Radical SAM Enzymes Involved in Methylation of Ribosomal RNA

2010 ◽  
Vol 132 (11) ◽  
pp. 3953-3964 ◽  
Author(s):  
Feng Yan ◽  
Jacqueline M. LaMarre ◽  
Rene Röhrich ◽  
Jochen Wiesner ◽  
Hassan Jomaa ◽  
...  
Keyword(s):  
Ribosomal Rna ◽  
Radical Sam ◽  
Radical Sam Enzymes

scholarly journals H-cluster assembly intermediates built on HydF by the radical SAM enzymes HydE and HydG

2019 ◽  
Vol 24 (6) ◽  
pp. 783-792 ◽  
Author(s):  
Amanda S. Byer ◽  
Eric M. Shepard ◽  
Michael W. Ratzloff ◽  
Jeremiah N. Betz ◽  
Paul W. King ◽  
...  
Keyword(s):  
Cluster Assembly ◽  
Radical Sam ◽  
Radical Sam Enzymes

scholarly journals Thioether bond formation by SPASM domain radical SAM enzymes: Cα H-atom abstraction in subtilosin A biosynthesis

2016 ◽  
Vol 52 (37) ◽  
pp. 6249-6252 ◽  
Author(s):  
Alhosna Benjdia ◽  
Alain Guillot ◽  
Benjamin Lefranc ◽  
Hubert Vaudry ◽  
Jérôme Leprince ◽  
...  
Keyword(s):  
Bond Formation ◽  
Radical Sam ◽  
Radical Sam Enzymes ◽  
Radical Sam Enzyme ◽  
Synthetic Approaches

The radical SAM enzyme AlbA has been reported to catalyze the formation of a thioether bond in the antibiotic subtilosin A. By modeling, biochemical and synthetic approaches, we propose novel mechanistic perspectives on this emerging group of enzymes.

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