Nature Search

Cooperative organization in a macromolecular complex

Markus A Seeliger
Sadie E Breward
Laura S Itzhaki
Research03 Aug 2003
Nature Structural & Molecular Biology

Volume: 10, P: 718-724
Erratum: Cooperative organization in a macromolecular complex

Markus A Seeliger
Sadie E Breward
Laura S Itzhaki
Amendments and Corrections01 Jul 2004
Nature Structural & Molecular Biology

Volume: 11, P: 678
Structural mechanism of a drug-binding process involving a large conformational change of the protein target

Atomic-level descriptions of protein–small molecule binding processes that involve a large conformational change of the protein have been elusive. Here, the authors report unguided molecular dynamics simulations of such a process—Abl kinase binding the cancer drug imatinib.

Pelin Ayaz
Agatha Lyczek
David E. Shaw
ResearchOpen Access05 Apr 2023
Nature Communications

Volume: 14, P: 1-15
An allosteric add-on

Development of highly specific kinase inhibitors has been a long-standing challenge in chemical biology. The structural and mechanistic characterization of an Erk1/2 kinase inhibitor provides new strategies to develop specific kinase inhibitors by targeting a binding pocket adjacent to the ATP binding site.

Zachariah H Foda
Markus A Seeliger
News & Views07 Sept 2014
Nature Chemical Biology

Volume: 10, P: 796-797
Discovery and molecular basis of subtype-selective cyclophilin inhibitors

DNA-templated compound library screening and structure-guided hit optimization resulted in the identification of selective macrocyclic inhibitors of cyclophilin isoforms CypD and CypE.

Alexander A. Peterson
Aziz M. Rangwala
David R. Liu
ResearchOpen Access26 Sept 2022
Nature Chemical Biology

Volume: 18, P: 1184-1195
Substrate-selective inhibitors that reprogram the activity of insulin-degrading enzyme

High-throughput screening identifies compounds that target insulin-degrading enzyme (IDE) and X-ray co-crystallography reveals how these compounds block insulin degradation by IDE but support its proteolysis of other substrates, including glucagon.

Juan Pablo Maianti
Grace A. Tan
David R. Liu
Research13 May 2019
Nature Chemical Biology

Volume: 15, P: 565-574
A dynamically coupled allosteric network underlies binding cooperativity in Src kinase

Protein tyrosine kinases are subject to multiple regulatory mechanisms. Foda et al. show that reactants and products of the tyrosine kinase Src bind its catalytic domain with opposite cooperativity, and identify an allosteric network of dynamically coupled amino acids that underlie this behaviour.

Zachariah H. Foda
Yibing Shan
Markus A. Seeliger
ResearchOpen Access20 Jan 2015
Nature Communications

Volume: 6, P: 1-10
Survey of solution dynamics in Src kinase reveals allosteric cross talk between the ligand binding and regulatory sites

Src is a prototypical signaling non-receptor protein tyrosine kinase that interconverts between distinct conformations. Here the authors use variants of the kinase-inhibitor dasatinib to define three specific conformational states of the Src kinase and shed insight on the effect of conformation-specific inhibitors on Src dynamics.

Michael Tong
Jeff G. Pelton
Markus A. Seeliger
ResearchOpen Access18 Dec 2017
Nature Communications

Volume: 8, P: 1-15
SHP2 as a primordial epigenetic enzyme expunges histone H3 pTyr-54 to amend androgen receptor homeostasis

SHP2 interacts with ACK1 kinase to erase pY54-H3 (Tyr54-phosphorylation of histones H3) epigenetic marks and triggers Androgen receptor transcriptional program. It explains genital abnormalities and infertility in LEOPARD syndrome patients, and AR upregulation in prostate cancer.

Surbhi Chouhan
Dhivya Sridaran
Nupam P. Mahajan
ResearchOpen Access04 Jul 2024
Nature Communications

Volume: 15, P: 1-19
Inhibiting ACK1-mediated phosphorylation of C-terminal Src kinase counteracts prostate cancer immune checkpoint blockade resistance

Immune checkpoint blockade is showing promise in cancer immune therapy, but many solid tumours are resistant. Authors here identify a pathway in T cells that leads to increased activity of C-terminal Src kinase, a negative regulator of T cell activity, thus disabling tumour infiltrating T cells and causing immune therapy resistance.

Dhivya Sridaran
Surbhi Chouhan
Nupam P. Mahajan
ResearchOpen Access14 Nov 2022
Nature Communications

Volume: 13, P: 1-21
Highly specific, bisubstrate-competitive Src inhibitors from DNA-templated macrocycles

DNA-templated macrocycles bind the ATP binding pocket of Src kinase, locking it into an inactive conformation. These small-molecule inhibitors compete with both ATP and substrate for binding and inhibit the T338I gatekeeper mutant version of Src.

George Georghiou
Ralph E Kleiner
Markus A Seeliger
Research19 Feb 2012
Nature Chemical Biology

Volume: 8, P: 366-374
Targeting Bcr–Abl by combining allosteric with ATP-binding-site inhibitors

GNF-2 is a recently discovered, selective allosteric Bcr–Abl inhibitor. Solution NMR, X-ray crystallography, mutagenesis and hydrogen exchange mass spectrometry are now used to show that GNF-2 binds to the myristate-binding site of Abl, leading to changes in the structural dynamics of the ATP-binding site. The results show that the combination of allosteric and ATP-competitive inhibitors can overcome resistance to either agent alone.

Jianming Zhang
Francisco J. Adrián
Nathanael S. Gray
Research13 Jan 2010
Nature

Volume: 463, P: 501-506
Divergent allosteric control of the IRE1α endoribonuclease using kinase inhibitors

A kinase inhibitor based on a known type II inhibitor allosterically inhibits the RNase activity of IRE1α in vitro and in cells via the ATP-binding site in the kinase domain.

Likun Wang
B Gayani K Perera
Dustin J Maly
Research21 Oct 2012
Nature Chemical Biology

Volume: 8, P: 982-989
Activation of tyrosine kinases by mutation of the gatekeeper threonine

Substitution of the active site gatekeeper residue in the BCR-ABL oncoprotein and related kinases is a common mechanism of imanitib resistance but has also been observed in drug-naïve patients. New work suggests that this residue stabilizes a hydrophobic spine that links the N and C kinase lobes, promoting the active conformation, and that adverse mutations at the gatekeeper residue further stabilize the spine. Disruption of the spine would be an attractive new goal in drug development.

Mohammad Azam
Markus A Seeliger
George Q Daley
Research14 Sept 2008
Nature Structural & Molecular Biology

Volume: 15, P: 1109-1118
A conserved mechanism of DEAD-box ATPase activation by nucleoporins and InsP₆ in mRNA export

Ben Montpetit
Nathan D. Thomsen
Karsten Weis
Research27 Mar 2011
Nature

Volume: 472, P: 238-242
Migratory and anti-fibrotic programmes define the regenerative potential of human cardiac progenitors

In this study, the authors report that pluripotent stem cell-derived ventricular progenitors target loss of myocardium and fibrotic scarring to promote heart regeneration, thus offering new potential therapeutic strategies for heart injury.

Christine M. Poch
Kylie S. Foo
Karl-Ludwig Laugwitz
ResearchOpen Access12 May 2022
Nature Cell Biology

Volume: 24, P: 659-671
Anti-diabetic activity of insulin-degrading enzyme inhibitors mediated by multiple hormones

The discovery of a selective, physiologically active inhibitor of insulin-degrading enzyme (IDE) illuminates the therapeutic potential of IDE inhibitors for the treatment of diabetes and reveals that IDE regulates in vivo glucagon and amylin, in addition to insulin.

Juan Pablo Maianti
Amanda McFedries
David R. Liu
Research21 May 2014
Nature

Volume: 511, P: 94-98
Absence of ABL1 exon 2-encoded SH3 residues in BCR::ABL1 destabilizes the autoinhibited kinase conformation and confers resistance to asciminib

Ariel Leyte-Vidal
RosaAnna DeFilippis
Neil P. Shah
ResearchOpen Access31 Jul 2024
Leukemia

Volume: 38, P: 2046-2050

Search

Cooperative organization in a macromolecular complex

Erratum: Cooperative organization in a macromolecular complex

Structural mechanism of a drug-binding process involving a large conformational change of the protein target

An allosteric add-on

Discovery and molecular basis of subtype-selective cyclophilin inhibitors

Substrate-selective inhibitors that reprogram the activity of insulin-degrading enzyme

A dynamically coupled allosteric network underlies binding cooperativity in Src kinase

Survey of solution dynamics in Src kinase reveals allosteric cross talk between the ligand binding and regulatory sites

SHP2 as a primordial epigenetic enzyme expunges histone H3 pTyr-54 to amend androgen receptor homeostasis

Inhibiting ACK1-mediated phosphorylation of C-terminal Src kinase counteracts prostate cancer immune checkpoint blockade resistance

Highly specific, bisubstrate-competitive Src inhibitors from DNA-templated macrocycles

Targeting Bcr–Abl by combining allosteric with ATP-binding-site inhibitors

Divergent allosteric control of the IRE1α endoribonuclease using kinase inhibitors

Activation of tyrosine kinases by mutation of the gatekeeper threonine

A conserved mechanism of DEAD-box ATPase activation by nucleoporins and InsP₆ in mRNA export

Migratory and anti-fibrotic programmes define the regenerative potential of human cardiac progenitors

Anti-diabetic activity of insulin-degrading enzyme inhibitors mediated by multiple hormones

Absence of ABL1 exon 2-encoded SH3 residues in BCR::ABL1 destabilizes the autoinhibited kinase conformation and confers resistance to asciminib

Search

Quick links

Search

Filter By:

Search

Quick links