Month: February 2018

Second-generation CK2α inhibitors targeting the αD pocket

Jessica Iegre, Paul Brear, Claudia De Fusco, Masao Yoshida, Sophie L. Mitchell, Maxim Rossmann, Laura Carro Santos, Hannah F. Sore, Marko Hyvӧnen and David R. Spring

Chemical Science (2018) (9:3041-)
DOI: 10.1039/C7SC05122K
Pubmed: 29732088

PDB coordinates:

6EHU (3D view ), 5OTQ (3D view ), 5OTY (3D view ), 6EHK (3D view ), 5OTI (3D view ), 5OTL (3D view ), 5OTO (3D view ), 5OYF (3D view ), 5OSZ (3D view ), 5OT5 (3D view ), 5OTD (3D view ), 5OTH (3D view ), 5OT6 (3D view ), 5OUE (3D view ), 5OUM (3D view ), 5OUU (3D view ), 5OS8 (3D view ), 5OTR (3D view ), 6EII (3D view ), 5OQU (3D view ), 5ORK (3D view ), 5OSL (3D view ), 5OUL (3D view ), 5ORH (3D view ), 5ORJ (3D view ), 5OS7 (3D view )


CK2 is a critical cell cycle regulator that also promotes various anti-apoptotic mechanisms. Development of ATP-non-competitive inhibitors of CK2 is a very attractive strategy considering that the ATP binding site is highly conserved among other kinases. We have previously utilised a pocket outside the active site to develop a novel CK2 inhibitor, CAM4066. Whilst CAM4066 bound to this new pocket it was also interacting with the ATP site: herein, we describe an example of a CK2α inhibitor that binds completely outside the active site. Continue reading →

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Structural and Mechanistic Analysis of the Choline Sulfatase from Sinorhizobium melliloti: A Class I Sulfatase Specific for an Alkyl Sulfate Ester

Bert van Loo, Markus Schober, Eugene Valkov, Magdalena Heberlein, Erich Bornberg-Bauer, Kurt Faber, Marko Hyvönen, Florian Hollfelder

Journal of Molecular Biology, 430:1004-1023, 2018 
DOI: 10.1016/j.jmb.2018.02.010
Pubmed: 29458126
PDB coordinates:
6FNY (3D view )



Hydrolysis of organic sulfate esters proceeds by two distinct mechanisms, water attacking at either sulfur (S-O bond cleavage) or carbon (C-O bond cleavage). In primary and secondary alkyl sulfates attack at carbon is favored, whereas in aromatic sulfates and sulfated sugars attack at sulfur is preferred. This mechanistic distinction is mirrored in the classification of enzymes that catalyze sulfate ester hydrolysis: arylsulfatases catalyze S-O cleavage in sulfate sugars and arylsulfates and alkyl sulfatases break the C-O bond of alkyl sulfates. Continue reading →

Posted by Marko in Publications, 0 comments