Macromolecular room temperature crystallography

M Fischer - Quarterly Reviews of Biophysics, 2021 - cambridge.org
X-ray crystallography enables detailed structural studies of proteins to understand and
modulate their function. Conducting crystallographic experiments at cryogenic temperatures …

[HTML][HTML] NMR tools to detect protein allostery

O Gampp, H Kadavath, R Riek - Current Opinion in Structural Biology, 2024 - Elsevier
Allostery is a fundamental mechanism of cellular homeostasis by intra-protein
communication between distinct functional sites. It is an internal process of proteins to steer …

Room-temperature crystallography reveals altered binding of small-molecule fragments to PTP1B

TS Mehlman, JT Biel, SM Azeem, ER Nelson… - Elife, 2023 - elifesciences.org
Much of our current understanding of how small-molecule ligands interact with proteins
stems from X-ray crystal structures determined at cryogenic (cryo) temperature. For proteins …

Temperature artifacts in protein structures bias ligand-binding predictions

SYC Bradford, L El Khoury, Y Ge, M Osato… - Chemical …, 2021 - pubs.rsc.org
X-ray crystallography is the gold standard to resolve conformational ensembles that are
significant for protein function, ligand discovery, and computational methods development …

Assessment of enzyme active site positioning and tests of catalytic mechanisms through X-ray–derived conformational ensembles

F Yabukarski, JT Biel, MM Pinney… - Proceedings of the …, 2020 - National Acad Sciences
How enzymes achieve their enormous rate enhancements remains a central question in
biology, and our understanding to date has impacted drug development, influenced enzyme …

Large-scale ligand perturbations of the protein conformational landscape reveal state-specific interaction hotspots

TR Stachowski, M Fischer - Journal of Medicinal Chemistry, 2022 - ACS Publications
Protein flexibility is important for ligand binding but often ignored in drug design.
Considering proteins as ensembles rather than static snapshots creates opportunities to …

Pushed to extremes: distinct effects of high temperature versus pressure on the structure of STEP

L Guerrero, A Ebrahim, BT Riley, M Kim… - Communications …, 2024 - nature.com
Protein function hinges on small shifts of three-dimensional structure. Elevating temperature
or pressure may provide experimentally accessible insights into such shifts, but the effects of …

[PDF][PDF] FLEXR: automated multi-conformer model building using electron-density map sampling

TR Stachowski, M Fischer - Acta Crystallographica Section D …, 2023 - journals.iucr.org
Protein conformational dynamics that may inform biology often lie dormant in high-resolution
electron-density maps. While an estimated∼ 18% of side chains in high-resolution models …

Allosteric regulation of kinase activity in living cells

SS Godbole, NV Dokholyan - Elife, 2023 - elifesciences.org
The dysregulation of protein kinases is associated with multiple diseases due to the kinases'
involvement in a variety of cell signaling pathways. Manipulating protein kinase function, by …

[PDF][PDF] High-resolution double vision of the allosteric phosphatase PTP1B

S Sharma, T Skaist Mehlman… - … Section F: Structural …, 2024 - journals.iucr.org
Protein tyrosine phosphatase 1B (PTP1B) plays important roles in cellular homeostasis and
is a highly validated therapeutic target for multiple human ailments, including diabetes …