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The Structural Basis of ATP as an Allosteric Modulator

Shaoyong Lu, Wenkang Huang, Qi Wang, Qiancheng Shen, Shuai Li, Ruth Nussinov, Jian Zhang
2015 Biophysical Journal  
The synaptic vesicle protein Synaptotagmin I is the calcium ion sensor for neurotransmitter release. Synaptotagmins are comprised of C2 domains, calcium ion dependent, membrane-binding domains.  ...  They contain multiple C2 domains and all C2 domains are tethered to the membrane. Our recent work  ...  3Cpro and 3CDpro that have confounded virologists and structural biologists. 2671-Pos Board B101 The Structural Basis of ATP as an Allosteric Modulator Shaoyong Lu 1 , Wenkang Huang 1 , Qi Wang 1 ,  ... 
doi:10.1016/j.bpj.2014.11.2894 fatcat:2dbn7rswwbbkbfr576d32s5m5y

The Structural Basis of ATP as an Allosteric Modulator

Shaoyong Lu, Wenkang Huang, Qi Wang, Qiancheng Shen, Shuai Li, Ruth Nussinov, Jian Zhang, Guanghong Wei
2014 PLoS Computational Biology  
Recent findings uncovered the allosteric function of ATP in cellular signal transduction but little is understood about this critical behavior of ATP.  ...  part of ATP, with a small number from the adenine part of ATP.  ...  The role of ATP in cell signaling is known to serve not only as a substrate but also as an allosteric modulator.  ... 
doi:10.1371/journal.pcbi.1003831 pmid:25211773 pmcid:PMC4161293 fatcat:aujsntbymjea7nk76aw3jlpf2u

Molecular Dynamics Simulations Reveal the Mechanisms of Allosteric Activation of Hsp90 by Designed Ligands

Gerolamo Vettoretti, Elisabetta Moroni, Sara Sattin, Jiahui Tao, David A. Agard, Anna Bernardi, Giorgio Colombo
2016 Scientific Reports  
We examine the impact of different allosteric modulators on the stability, structural and internal dynamics properties of Hsp90 closed state.  ...  The underlying challenge is to design new molecular entities able to act as allosteric chemical switches that selectively turn on/off functions by modulating the conformational dynamics of their target  ...  Associazione Italiana Ricerca sul Cancro) grant IG 15420; we acknowledge funding from Fondazione Cariplo through grant 2011.1800, Premio Fondazione Cariplo per la ricerca di frontiera; we also acknowledge the  ... 
doi:10.1038/srep23830 pmid:27032695 pmcid:PMC4817115 fatcat:duidpjdxr5dxnjeyx7qihdew3i

Mapping Co-regulation Pathways among Ligand Binding sites in RyR1 [article]

Venkat R Chirasani, Konstantin I Popov, Gerhard Meissner, Nikolay V Dokholyan
2019 bioRxiv   pre-print
Such coordination of allosteric pathway underlies the molecular basis of synergy of channel regulation by multiple activators.  ...  Here, we report the detailed network of allosteric connections between the three ligand sites and the pore region in (i) Ca2+ bound - closed, (ii) ATP/CFF bound - closed, (iii) Ca2+/ATP/CFF bound - closed  ...  Jian Wang for developing an interactive web-server to depict graph-inspired pathways in RyR1. N.V.D. acknowledges the NIH support grants R01GM114015 and R01GM123247.  ... 
doi:10.1101/676841 fatcat:ppqcbx2wavg63ebbpyi5hpylge

P2X4 Receptor in Silico and Electrophysiological Approaches Reveal Insights of Ivermectin and Zinc Allosteric Modulation

Verónica Latapiat, Felipe E. Rodríguez, Francisca Godoy, Felipe A. Montenegro, Nelson P. Barrera, Juan P. Huidobro-Toro
2017 Frontiers in Pharmacology  
Energy calculations demonstrated a favorable transition of the holo receptor state following both allosteric modulators binding, as expected for allosteric interactions.  ...  increase in the ATP-gated currents. In summary, allosteric modulators caused additive ATP-gated currents; consistent with lateral fenestration enlargement.  ...  Lorca et al., 2005; Huidobro-Toro et al., 2008) , which are critical as structural elements to understand receptor topology and its molecular basis of allosteric modulation (Cully et al., 1994; Vassilatis  ... 
doi:10.3389/fphar.2017.00918 pmid:29326590 pmcid:PMC5737101 fatcat:fskjreivijf6vpieuo3tljgkjm

Proposed Thermodynamic Basis for Synaptotagmin Response

Anne Hinderliter
2015 Biophysical Journal  
The synaptic vesicle protein Synaptotagmin I is the calcium ion sensor for neurotransmitter release. Synaptotagmins are comprised of C2 domains, calcium ion dependent, membrane-binding domains.  ...  They contain multiple C2 domains and all C2 domains are tethered to the membrane. Our recent work  ...  3Cpro and 3CDpro that have confounded virologists and structural biologists. 2671-Pos Board B101 The Structural Basis of ATP as an Allosteric Modulator Shaoyong Lu 1 , Wenkang Huang 1 , Qi Wang 1 ,  ... 
doi:10.1016/j.bpj.2014.11.2892 fatcat:vdqkg3skkfelhhjclweyu2etvu

Towards comprehensive allosteric control over protein activity [article]

Enrico Guarnera, Igor N. Berezovsky
2018 bioRxiv   pre-print
Allosteric Signaling Maps (ASMs) obtained on the basis of residue-by-residue scanning are proposed as a comprehensive tool to explore a relationship between mutations allosterically modulating protein  ...  On the basis of the perturbation nature of allosteric communication, a computational framework is proposed for estimating the energetics of signaling caused by the ligand binding and mutations.  ...  existing allosteric signaling with effects of mutations, as well as by designing new elements of regulation on the basis of allosteric signals of individual mutations and their combinations.  ... 
doi:10.1101/384198 fatcat:se5tbgtahbe2hfqxxgdmvj4koy

Molecular Mechanism of Allosteric Communication in Hsp70 Revealed by Molecular Dynamics Simulations

Federica Chiappori, Ivan Merelli, Giorgio Colombo, Luciano Milanesi, Giulia Morra, Qiang Cui
2012 PLoS Computational Biology  
The Hsp70 family of chaperones represents an example of proteins in which ATP binding and hydrolysis at the Nucleotide Binding Domain (NBD) modulate substrate recognition at the Substrate Binding Domain  ...  Herein, a comparative analysis of an allosteric (Hsp70-DnaK) and a non-allosteric structural homolog (Hsp110-Sse1) of the Hsp70 family is carried out through molecular dynamics simulations, starting from  ...  In contrast, the X-ray structure of yeast Hsp110, a structural homolog of Hsp70, shows an ATP-bound open conformation [12] .  ... 
doi:10.1371/journal.pcbi.1002844 pmid:23300424 pmcid:PMC3531320 fatcat:dooznx6bdvcytgx77bp5uy6fv4

αC helix displacement as a general approach for allosteric modulation of protein kinases

Lorenzo Palmieri, Giulio Rastelli
2013 Drug Discovery Today  
The classic approach of targeting the ATP active site has recently come up against selectivity issues, which can be considerably reduced by following an allosteric modulation approach.  ...  A structure-based survey of the allosteric regulation of aC helix conformation in various kinase families is provided, highlighting key allosteric pockets and modulation mechanisms that appear to be more  ...  The analysis is also limited to kinase targets for which allosteric modulation mechanisms have been proven on structural grounds, on the basis of crystal structures deposited in the PDB.  ... 
doi:10.1016/j.drudis.2012.11.009 pmid:23195331 fatcat:gqj33mpktrcsldqo4qonritqgi

Drugs for Allosteric Sites on Receptors

Cody J. Wenthur, Patrick R. Gentry, Thomas P. Mathews, Craig W. Lindsley
2014 Annual Review of Pharmacology and Toxicology  
As the field has matured, as described here, key principles and strategies have emerged for the design of ligands/drugs for allosteric sites.  ...  Many allosteric ligands possess molecular switches, wherein a small structural change (chemical or metabolic) can modulate the mode of pharmacology or receptor subtype selectivity.  ...  Acknowledgments The authors thank Janssen Pharmaceuticals (Johnson & Johnson), Bristol-Myers Squibb, AstraZeneca, the National Institutes of Health, the National Institute of Mental Health, and the National  ... 
doi:10.1146/annurev-pharmtox-010611-134525 pmid:24111540 pmcid:PMC4063350 fatcat:6pasehmtzrhl5ogjrczqqrhbm4

Allosteric Functional Switch in Poliovirus 3C Protease

Yan M. Chan, David D. Boehr
2015 Biophysical Journal  
The synaptic vesicle protein Synaptotagmin I is the calcium ion sensor for neurotransmitter release. Synaptotagmins are comprised of C2 domains, calcium ion dependent, membrane-binding domains.  ...  They contain multiple C2 domains and all C2 domains are tethered to the membrane. Our recent work  ...  3Cpro and 3CDpro that have confounded virologists and structural biologists. 2671-Pos Board B101 The Structural Basis of ATP as an Allosteric Modulator Shaoyong Lu 1 , Wenkang Huang 1 , Qi Wang 1 ,  ... 
doi:10.1016/j.bpj.2014.11.2893 fatcat:al2ul6j36ngojo4kwxmi6l756q

Two Pathways Mediate Inter-Domain Allosteric Regulation in Pin1

Jingjing Guo, Xiaodong Pang, Huan-Xiang Zhou
2015 Biophysical Journal  
The synaptic vesicle protein Synaptotagmin I is the calcium ion sensor for neurotransmitter release. Synaptotagmins are comprised of C2 domains, calcium ion dependent, membrane-binding domains.  ...  They contain multiple C2 domains and all C2 domains are tethered to the membrane. Our recent work  ...  3Cpro and 3CDpro that have confounded virologists and structural biologists. 2671-Pos Board B101 The Structural Basis of ATP as an Allosteric Modulator Shaoyong Lu 1 , Wenkang Huang 1 , Qi Wang 1 ,  ... 
doi:10.1016/j.bpj.2014.11.2896 fatcat:slu63ykryvgcpbcr223b75wbiq

The Impact of Perturbing Dynamic Amino Acid Networks in a (β/α)8 Barrel Enzyme

Kathleen F. O'Rourke, Jennifer M. Axe, Nicole E. Kerstetter, David D. Boehr
2015 Biophysical Journal  
The synaptic vesicle protein Synaptotagmin I is the calcium ion sensor for neurotransmitter release. Synaptotagmins are comprised of C2 domains, calcium ion dependent, membrane-binding domains.  ...  They contain multiple C2 domains and all C2 domains are tethered to the membrane. Our recent work  ...  3Cpro and 3CDpro that have confounded virologists and structural biologists. 2671-Pos Board B101 The Structural Basis of ATP as an Allosteric Modulator Shaoyong Lu 1 , Wenkang Huang 1 , Qi Wang 1 ,  ... 
doi:10.1016/j.bpj.2014.11.2897 fatcat:5ufeea6m3ncnzczphzvtezqeoi

Geometric Description of Dynamin Induced Membrane Fission

Pablo Vázquez-Montejo, Zachary McDargh, Markus Deserno
2015 Biophysical Journal  
The synaptic vesicle protein Synaptotagmin I is the calcium ion sensor for neurotransmitter release. Synaptotagmins are comprised of C2 domains, calcium ion dependent, membrane-binding domains.  ...  They contain multiple C2 domains and all C2 domains are tethered to the membrane. Our recent work  ...  3Cpro and 3CDpro that have confounded virologists and structural biologists. 2671-Pos Board B101 The Structural Basis of ATP as an Allosteric Modulator Shaoyong Lu 1 , Wenkang Huang 1 , Qi Wang 1 ,  ... 
doi:10.1016/j.bpj.2014.11.2895 fatcat:ags2qdfu6bhkfcyks37vwgyh7q

Use of Allosteric Targets in the Discovery of Safer Drugs

Ashok Kumar Grover
2013 Medical Principles and Practice  
A new basis of drug discovery is emerging based on the binding of the drug molecules to sites away (allosteric) from the orthosteric sites.  ...  Exploitation of allosteric sites has led to the discovery of drugs which can selectively modulate the activation of only 1 (M1 muscarinic) out of the 12 different types of acetylcholine receptors.  ...  ATP)ase [3] .  ... 
doi:10.1159/000350417 pmid:23711993 pmcid:PMC5586781 fatcat:75jchqebifbvzccprwdwxq7n2y
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