S. Knapp

Structure-based design of selective salt-inducible kinase (SIK) inhibitors

This study designs a selective SIK inhibitor, MRIA9, based on a PAK inhibitor, showing its dual activity and potential for combination therapy in ovarian cancer.

Phylogenomic discordance suggests polytomies along the backbone of the large genus Solanum

The paper investigates gene-tree discordance in Solanum, finding polytomies along its backbone due to rapid diversification and incomplete lineage sorting.

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.

Murine ex vivo cultured alveolar macrophages provide a novel tool to study tissue-resident macrophage behavior and function

This paper introduces a method to culture and expand murine alveolar macrophages ex vivo over several months, showing they retain key features and functions.

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.

Deciphering the LRRK code: LRRK1 and LRRK2 phosphorylate distinct Rab proteins and are regulated by diverse mechanisms

This study identifies distinct Rab proteins phosphorylated by LRRK1 and LRRK2, showing they are regulated by different mechanisms and respond differently to inhibitors.

Conformation and dynamics of the kinase domain drive subcellular location and activation of LRRK2

This study investigates how Parkinson's Disease mutations affect LRRK2 activation and subcellular localization through conformational changes and domain interactions.

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.

Optimization of pyrazolopyrimidines lead to the identification of a highly selective casein kinase 2 inhibitor

This paper describes the optimization of pyrazolopyrimidine compounds to develop a highly selective and potent CK2 inhibitor, IC20, with high in vitro potency and exclusive selectivity.

Nucleotide binding, evolutionary insights and interaction partners of the pseudokinase Unc-51-like kinase 4

This study presents the structure of ULK4-ATPγS complex, identifies disease mutations affecting ATP binding, and reveals ULK4's interaction partners and evolutionary adaptations.

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.

A Highly Selective Chemical Probe for Activin Receptor-like Kinases ALK4 and ALK5

The paper develops a selective chemical probe, TP-008, for ALK4 and ALK5 kinases and provides a negative control, enabling mechanistic studies of their signaling pathway and disease roles.

Parkinson's Disease-linked LRRK2 structure and model for microtubule interaction

This study reports the structure of LRRK2 and its interaction with microtubules, showing that its conformation regulates binding and affects motor protein function.

The Kinase Chemogenomic Set (KCGS): An open science resource for kinase vulnerability identification

The paper introduces the Kinase Chemogenomic Set (KCGS), a curated collection of 187 selective kinase inhibitors covering 215 human kinases, for use in cell-based screens.

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.

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.

Dynamism and context dependency in the diversification of the megadiverse plant genus Solanum L. (Solanaceae).

The paper examines how dispersal events and climatic changes have shaped the diversification of the plant genus Solanum, finding that Old World lineages are diversifying more rapidly following a long-distance dispersal event.

A Chemical Toolbox for the Study of Bromodomains and Epigenetic Signaling

The paper presents a set of 25 chemical probes targeting human bromodomains and demonstrates their utility in studying muscle cell differentiation and triple negative breast cancer.

SGC-GAK-1: a chemical probe for cyclin G associated kinase (GAK)

The paper describes SGC-GAK-1, a selective GAK inhibitor, and identifies a related compound that inhibits RIPK2 without GAK activity, providing tools to study GAK and RIPK2 biology.

Identifying small molecule binding sites for epigenetic proteins at domain-domain interfaces

The paper identifies potential small molecule binding sites at domain-domain interfaces of epigenetic proteins using computational and experimental methods.

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.

North Andean origin and diversification of the largest ithomiine butterfly genus

This study uses molecular and morphological data to reconstruct the phylogeny of the butterfly genus Pteronymia, showing its origin in the Northern Andes and diversification patterns.

Progress Towards a Public Chemogenomic Set for Protein Kinases and a Call for Contributions

The paper shares progress on a kinase chemogenomic set, releases inhibitor profiling data, and calls for community collaboration to complete the set.