scholarly journals γ-Secretase Inhibitors and Modulators Induce Distinct Conformational Changes in the Active Sites of γ-Secretase and Signal Peptide Peptidase

2015 ◽  
Vol 10 (8) ◽  
pp. 1925-1931 ◽  
Author(s):  
Natalya Gertsik ◽  
De-Ming Chau ◽  
Yue-Ming Li
Keyword(s):  
Conformational Changes ◽  
Signal Peptide ◽  
Active Sites ◽  
Signal Peptide Peptidase

scholarly journals Vigilin interacts with signal peptide peptidase

2012 ◽  
Vol 10 (1) ◽  
pp. 33 ◽  
Author(s):  
Stephen Hsueh-Jeng Lu ◽  
Amy Hye Won Jeon ◽  
Gerold Schmitt-Ulms ◽  
Seema Qamar ◽  
Roger Dodd ◽  
...  
Keyword(s):  
Signal Peptide ◽  
Signal Peptide Peptidase

scholarly journals Signal peptide peptidase activity connects the unfolded protein response to plant defense suppression by Ustilago maydis

2019 ◽  
Vol 15 (4) ◽  
pp. e1007734 ◽  
Author(s):  
Niko Pinter ◽  
Christina Andrea Hach ◽  
Martin Hampel ◽  
Dmitrij Rekhter ◽  
Krzysztof Zienkiewicz ◽  
...  
Keyword(s):  
Plant Defense ◽  
Unfolded Protein Response ◽  
Signal Peptide ◽  
Ustilago Maydis ◽  
Peptidase Activity ◽  
Signal Peptide Peptidase ◽  
Unfolded Protein ◽  
The Unfolded Protein Response ◽  
Protein Response

scholarly journals Role of allosteric switches and adaptor domains in long-distance cross-talk and transient tunnel formation

2020 ◽  
Vol 6 (14) ◽  
pp. eaay7919
Author(s):  
Nandini Sharma ◽  
Navjeet Ahalawat ◽  
Padmani Sandhu ◽  
Erick Strauss ◽  
Jagannath Mondal ◽  
...  
Keyword(s):  
Conformational Changes ◽  
Active Sites ◽  
Long Distance ◽  
Dynamic Interactions ◽  
Interface Control ◽  
Protein Energy ◽  
Catalytic Loop ◽  
Ammonia Tunnel ◽  
Dynamics Simulations

Transient tunnels that assemble and disassemble to facilitate passage of unstable intermediates in enzymes containing multiple reaction centers are controlled by allosteric cues. Using the 140-kDa purine biosynthetic enzyme PurL as a model system and a combination of biochemical and x-ray crystallographic studies, we show that long-distance communication between ~25-Å distal active sites is initiated by an allosteric switch, residing in a conserved catalytic loop, adjacent to the synthetase active site. Further, combinatory experiments seeded from molecular dynamics simulations help to delineate transient states that bring out the central role of nonfunctional adaptor domains. We show that carefully orchestrated conformational changes, facilitated by interplay of dynamic interactions at the allosteric switch and adaptor-domain interface, control reactivity and concomitant formation of the ammonia tunnel. This study asserts that substrate channeling is modulated by allosteric hotspots that alter protein energy landscape, thereby allowing the protein to adopt transient conformations paramount to function.

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