A. Chaikuad

Modulation of Tau Tubulin Kinases (TTBK1 and TTBK2) Impacts Ciliogenesis

The paper identifies chemical tools that inhibit TTBK1 and TTBK2, showing that TTBK2 inhibition reduces ciliogenesis in iPSCs.

Structural insights into plasticity and discovery of remdesivir metabolite GS-441524 binding in SARS-CoV-2 macrodomain

The paper reports crystal structures of SARS-CoV-2 nsP3 macrodomain bound to nucleotides and remdesivir metabolites, revealing structural plasticity and potential inhibitor targets.

Structure and inhibitor binding characterization of oncogenic MLLT1 mutants

The paper reports crystal structures of oncogenic MLLT1 mutants, showing conformational changes and altered histone binding, but demonstrates that these mutants can still be targeted by acetyllysine mimetic inhibitors.

DFG-1 residue controls inhibitor binding mode and affinity providing a basis for rational design of kinase inhibitor selectivity

The paper identifies DFG-1 residues as a target for designing selective kinase inhibitors with non-canonical binding modes, showing that bulky DFG-1 residues enable selectivity over smaller ones.

Catalytic domain plasticity of MKK7 reveals structural mechanisms of allosteric activation and new targeting opportunities

This study presents MKK7 crystal structures and identifies new allosteric targets, revealing structural mechanisms of activation and potential drug candidates.

STK32A is a dual-specificity AGC kinase with a preference for acidic substrates

This study identifies STK32A as a dual-specificity AGC kinase preferring acidic substrates, revealing structural and evolutionary features supporting its substrate specificity.

Structural insights into interaction mechanisms of alternative piperazine-urea YEATS domain binders in MLLT1

The paper characterizes piperazine-urea derivatives as acetyl/acyl-lysine mimetics for MLLT1 and reveals distinct interaction mechanisms through crystal structures.

p63 sets the threshold for induction of apoptosis using a kinetically encoded ‘doorbell-like’ mechanism

The paper shows that TAp63 uses a slow third phosphorylation step to set a threshold for apoptosis induction in response to DNA damage.

Conservation of structure, function and inhibitor binding in UNC-51-like kinase 1 and 2 (ULK1/2)

The paper presents the crystal structure of ULK2 with ATP inhibitors, identifies off-target effects of ULK1 inhibitors, and suggests structural insights for developing dual ULK1/2 inhibitors.

Genetic, structural, and functional analysis of mutations causing methylmalonyl-CoA epimerase deficiency

The paper identifies ten new patients with MCEE deficiency, analyzes mutations in the MCEE gene, and reveals structural and functional defects in the enzyme caused by these mutations.

A structure-based approach towards identification of inhibitory fragments for eleven-nineteen-leukemia protein (ENL) YEATS domain

The paper identifies inhibitory fragments targeting the ENL YEATS domain using crystallography, providing starting points for chemical probe development.

Halogen-aromatic π-interactions modulate inhibitor residence time

The paper shows that halogen-aromatic π-interactions increase inhibitor residence time in kinase-inhibitor complexes, providing a strategy to improve drug efficacy and selectivity.