Toward Understanding the Structural Basis of Cyclin-Dependent Kinase 6 Specific Inhibition

2006 ◽  
Vol 49 (13) ◽  
pp. 3826-3831 ◽  
Author(s):  
Heshu Lu ◽  
Ursula Schulze-Gahmen
Keyword(s):  
Structural Basis ◽  
Specific Inhibition ◽  
Cyclin Dependent Kinase

scholarly journals Structural basis for context-specific inhibition of translation by oxazolidinone antibiotics

2021 ◽  
Author(s):  
Kaitlyn Tsai ◽  
Vanja Stojković ◽  
D. John Lee ◽  
Iris D. Young ◽  
Teresa Szal ◽  
...  
Keyword(s):  
Peptide Bond ◽  
Structural Basis ◽  
Side Chain ◽  
Specific Inhibition ◽  
Peptide Bond Formation ◽  
Peptidyl Transferase ◽  
Nascent Chain ◽  
Context Specific ◽  
Small Hydrophobic ◽  
Penultimate Position

The antibiotic linezolid, the first clinically approved member of the oxazolidinone class, inhibits translation of bacterial ribosomes by binding to the peptidyl transferase center. Recent work has demonstrated that linezolid does not inhibit peptide bond formation at all sequences but rather acts in a context-specific manner, namely when alanine occupies the penultimate position of the nascent chain. In this study, we determined that the second-generation oxazolidinone radezolid also induces stalling with alanine at the penultimate position. However, the molecular basis for context-specificity of these inhibitors has not been elucidated. In this study, we determined high-resolution cryo-EM structures of both linezolid and radezolid-stalled ribosome complexes. These structures reveal that the alanine side chain fits within a small hydrophobic crevice created by oxazolidinone, resulting in improved ribosome binding. Modification of the ribosome by the antibiotic resistance enzyme Cfr disrupts stalling by forcing the antibiotic to adopt a conformation that narrows the hydrophobic alanine pocket. Together, the structural and biochemical findings presented in this work provide molecular understanding of context-specific inhibition of translation by clinically important oxazolidinone antibiotics.

scholarly journals Structural basis of divergent cyclin‐dependent kinase activation by Spy1/ RINGO proteins

2017 ◽  
Vol 36 (15) ◽  
pp. 2251-2262 ◽  
Author(s):  
Denise A McGrath ◽  
Bre‐Anne Fifield ◽  
Aimee H Marceau ◽  
Sarvind Tripathi ◽  
Lisa A Porter ◽  
...  
Keyword(s):  
Structural Basis ◽  
Cyclin Dependent Kinase ◽  
Kinase Activation

Structural Basis of the Interaction of Cyclin-Dependent Kinase 2 with Roscovitine and Its Analogues Having Bioisosteric Central Heterocycles

ChemPhysChem ◽  
2017 ◽  
Vol 18 (7) ◽  
pp. 785-795 ◽  
Author(s):  
Michaela Nekardová ◽  
Ladislava Vymětalová ◽  
Prashant Khirsariya ◽  
Silvia Kováčová ◽  
Michaela Hylsová ◽  
...  
Keyword(s):  
Structural Basis ◽  
Cyclin Dependent Kinase

scholarly journals Structural Basis for Specific Inhibition of tRNA Synthetase by an ATP Competitive Inhibitor

2015 ◽  
Vol 22 (6) ◽  
pp. 734-744 ◽  
Author(s):  
Pengfei Fang ◽  
Hongyan Han ◽  
Jing Wang ◽  
Kaige Chen ◽  
Xin Chen ◽  
...  
Keyword(s):  
Competitive Inhibitor ◽  
Trna Synthetase ◽  
Structural Basis ◽  
Specific Inhibition

scholarly journals Structural basis for the specific inhibition of heterotrimeric Gq protein by a small molecule

2010 ◽  
Vol 107 (31) ◽  
pp. 13666-13671 ◽  
Author(s):  
A. Nishimura ◽  
K. Kitano ◽  
J. Takasaki ◽  
M. Taniguchi ◽  
N. Mizuno ◽  
...  
Keyword(s):  
Small Molecule ◽  
Structural Basis ◽  
Specific Inhibition
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