PSI Structural Biology Knowledgebase

PSI | Structural Biology Knowledgebase
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Cancer
Cell biology
DNA and RNA
Drug discovery
Epigenetics
Immunology
Infectious diseases
Membrane proteins
Microbiome
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Protein design
Protein-protein interactions

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Target Selection
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E-Collection Research Themes: Drug discovery

Related Articles

Design and Evolution: Molecular Sleuthing Reveals Drug Selectivity

Featured Article - June 2015
Reconstructed ancient ancestors of Src and Abl shed light on Gleevec's specificity.

Families in Gene Neighborhoods

Technical Highlight - June 2015
A bioinformatics strategy takes advantage of the proximal organization of genes encoding proteins involved in metabolic pathways to predict protein function.

Ryanodine Receptor

Featured System - April 2015
PSI researchers take a close look at a gated calcium channel that controls muscle contraction.

CCR5 and HIV Infection

Featured System - January 2015
A new PSI structure shows how the anti-HIV drug maraviroc locks the coreceptor CCR5 in an inactive state.

Drug Targets: Bile Acids in Motion

Featured Article - September 2014
Crystal structures of sodium-dependent bile acid transporters provide insight into transport mechanism.

Drug Targets: S1R's Ligands and Partners

Featured Article - September 2014
Stabilization of oligomers by small-molecule ligands suggests a mechanism for regulating a membrane protein chaperone.

P2Y Receptors and Blood Clotting

Featured System - September 2014
PSI researchers have revealed a novel rearrangement in a purine-binding GPCR, opening new avenues for the design of blood clotting drugs.

Bacterial CDI Toxins

Featured System - June 2014
PSI researchers have solved the structures of several potent bacterial toxins, along with their antidotes.

Glucagon Receptor

Featured System - April 2014
PSI researchers have solved the structures of a GPCR that binds to peptide hormones, revealing new modes of GPCR recognition.

Viroporins

Featured System - March 2014
PSI researchers have determined the structures of several viral pore-forming proteins, revealing common functional features.

Microbial Pathogenesis: Targeting Drug Resistance in Mycobacterium tuberculosis

Featured Article - February 2014
Whole-cell screening for antituberculosis compounds combined with identification of resistance-linked mutations provide novel scaffolds for drug development.

Design and Discovery: Virtual Drug Screening

Technical Highlight - January 2014
Optimized crystal structure-based models yield diverse hits in a virtual screen targeting G protein-coupled receptor allosteric and orthosteric ligand-binding sites.

Cancer Networks: IFI16-mediated p53 Activation

Featured Article - November 2013
Structural and functional analyses of the p53-binding HIN domains of IFI16 reveal their mechanism of action.

G Proteins and Cancer

Featured System - November 2013
G-proteins play an essential role in cell signaling, a role that is corrupted in many types of cancer cells.

Drug Discovery: Antidepressant Potential of 6-NQ SERT Inhibitors

Featured Article - October 2013
Molecular docking models are combined with in vitro and in vivo assays to evaluate the therapeutic potential of 6-nitroquipazine analogs as antidepressants.

Drug Discovery: Finding Druggable Targets

Technical Highlight - October 2013
A guide to selecting strategic targets for pharmacological intervention and drug design in microbiomes is presented for Streptococcus mutans.

Drug Discovery: Identifying Dynamic Networks by CONTACT

Technical Highlight - October 2013
A new automated algorithm uses X-ray data to identify dynamic contact networks involved in enzyme catalysis.

Drug Discovery: Modeling NET Interactions

Featured Article - October 2013
A structural model of the norepinephrine transporter is used in a virtual ligand screen to identify new drug interactions.

Membrane Proteome: GPCR Substrate Recognition and Functional Selectivity

Featured Article - August 2013
Crystal structures of 5-HT receptors bound to antimigraine drugs offer insights into ligand specificity and signaling bias.

Infectious Diseases: Determining the Essential Structome

Technical Highlight - May 2013
Twenty-five potential drug targets emerge from the Burkholderia structome through an integrated pipeline.

NDM-1 and Antibiotics

Featured System - May 2013
With structural biology and computational analysis, PSI Biology researchers have revealed the catalytic pathway of an antibiotic-destroying enzyme.

Microbial Pathogenesis: Computational Epitope Prediction

Technical Highlight - January 2013
A computational approach uses structural information to identify epitopes within antigenic proteins.

Microbial Pathogenesis: Influenza Inhibitor Screen

Technical Highlight - January 2013
A cell-free binding assay is optimized step by step and applied in high throughput to screen for small molecule inhibitors of an influenza protein.

Microbial Pathogenesis: Measles Virus Attachment

Featured Article - January 2013
The third structure of a host receptor bound to measles virus hemagglutinin pinpoints a hydrophobic lock hole.

Cytochrome Oxidase

Featured System - November 2012
Cytochrome oxidase is the foundation of aerobic respiration.

Membrane Proteome: The ABCs of Transport

Featured Article - November 2012
Structural analyses of two ABC transporters reveal how diverse transmembrane domain architectures determine substrate specificity and transport mechanisms.

Bacterial Phosphotransferase System

Featured System - October 2012
Bacteria are thrifty cells.

Regulatory insights

Featured Article - September 2012
Structures of the JH2 pseudokinase domain provide clues to its role in normal and disease-associated JAK signaling.

Solute Channels

Featured System - September 2012
Cells maintain a steady traffic of small molecules across their membranes.

Pocket changes

Technical Highlight - July 2012
Pocketome, an encyclopedia of small-molecule binding sites, helps analyze druggable sites.

Receptor bias

Featured Article - July 2012
Fluorine NMR characterization of the β2-adrenergic receptor uncovers conformational states that may bias GPCR signaling pathways.

Anthrax Stealth Siderophores

Featured System - June 2012
Iron is an essential mineral, used by many enzymes for its ability to trap small molecules like oxygen and to act as a conduit of electron transfer.

G Protein-Coupled Receptors

Featured System - May 2012
In the past five years, the field of GPCR structure has exploded.

Substrate specificity sleuths

Featured Article - April 2012
Crystal structures of constitutive and immunoproteasomes in the presence and absence of inhibitor reveal the structural basis for substrate and inhibitor specificity.

Reading out regioselectivity

Featured Article - December 2011
The structures of four glycosyltransferases operating within a single biosynthetic pathway point to conserved and divergent mechanisms for controlling the regioselective addition of sugar donors, with implications for glycosyltransferase engineering.

Superbugs and Antibiotic Resistance

Featured System - December 2011
Antibiotics were used as weapons to fight bacteria long before Alexander Fleming discovered penicillin.

Terminal activation

Featured Article - December 2011
The recent crystal structure of the human BIG2 Sec7 domain reveals a novel ARF-interacting motif that regulates ARF activation.

A change to resistance

Featured Article - November 2011
Two structures of NDM-1 β-lactamase show how this enzyme can confer resistance to many antibiotics.

Docking and rolling

Featured Article - October 2011
GPCR Dock 2010 reveals just how far homology modeling has come and how far it still has to go.

Breaking down the defenses

Featured Article - September 2011
The structure of ISG15 bound to NS1B gives insight into the mechanism by which influenza B virus specifically targets humans.

A2A Adenosine Receptor

Featured System - May 2011
With proteins, small motions often have large effects.

Cell wall recycler

Featured Article - May 2011
The crystal structure of the bacterial cell wall recycling protein Mpl reveals similarities as well as differences compared with functionally related Mur ligases.

Subtly different

Featured Article - March 2011
The crystal structure of the D3 dopamine receptor reveals how to selectively target D2-like receptors.

CXCR4

Featured System - January 2011
The GPCR (G protein-coupled receptor) community is suffering from an embarrassment of riches.

Subtle shifts

Featured Article - January 2011
The crystal structure of EF-Tu bound to the 70S ribosome solves a 40-year-old puzzle.

ABA receptor diversity

Featured Article - November 2010
There are 14 members in the ABA receptor family in Arabidopsis thaliana. How these receptors differ in their response to a synthetic, seed-specific ABA agonist is now explored in two independent papers, using a combination of crystallography, NMR and biochemical approaches.

COX inhibition: Naproxen by proxy

Featured Article - November 2010
Structural basis of COX inhibition suggests that adverse effects of NSAIDs will not be easily avoided.

Zinc Transporter ZntB

Featured System - July 2010
Zinc is an essential component of many cellular processes.

Peptidoglycan binding: Calcium-free killing

Featured Article - June 2010
NMR spectroscopy reveals the molecular basis for Ca2+-independent recognition by bactericidal Reg family lectins.

Treating sleeping sickness

Featured Article - May 2010
A potential new drug kills the bloodstream parasite that causes this disease.

Bacterial spore kinase

Featured Article - April 2010
A genomic, phylogenetic and structural study hints that these kinases have functional roles that might be druggable.

Antibiotics and Ribosome Function

Featured System - March 2010
Antibiotics are often discovered in nature, where they are lethal weapons in the fight between different organisms.

Safer Alzheimer's drugs?

Featured Article - March 2010
Inhibitors that only partially block phosphodiesterase activity look likely to reduce the nasty side effects of full inhibitors.

Anthrax evasion tactics

Featured Article - September 2009
The crystal structure of a crucial anthrax capsule enzyme will aid the search for new therapies.

GPCR subunits: Separate but not equal

Featured Article - September 2009
A functional complementation assay reveals that maximal heterotrimeric G-protein activation is achieved by agonist binding to one subunit of a dopamine D2 receptor dimer.

Antibiotic target

Featured Article - August 2009
An unusual reaction in the production of thymine offers hope for anti-tuberculosis drugs.Nature 458, 919-923 (2009)

Salicylic Acid Binding Protein 2

Featured System - August 2009
Centuries ago, both the ancient Greeks and native Americans discovered that willow bark and other plants can dull pain.

Lysostaphin

Featured System - July 2009
Antibiotics are one of the major triumphs of twentieth century science, but unfortunately, the bacteria are fighting back.

Tackling influenza

Featured Article - June 2009
Structural studies reveal a new target for anti-influenza drugs that should work whatever the influenza virus strain.Nature 458, 909-913 (2009)

Bacterial Leucine Transporter, LeuT

Featured System - May 2009
Many antidepressant drugs, as well as drugs of abuse such as cocaine, block the traffic of neurotransmitters across the cell membrane of nerve axons and glial cells.

Anthrax stealth molecule

Featured Article - March 2009
Bacillus anthracis relies on an unusual metabolite to evade human innate immunity and to be fully virulent in the host.Proc. Natl Acad. Sci. USA 105, 17133-17138 (2008)

Drug targets to aim for

Technical Highlight - February 2009
The TDR Targets database combines genomic data on tropical-disease pathogens with structural and biochemical information to help researchers draw up a shortlist of potential drug targets.Nature Rev. Drug Disc. 7, 900-907 (2008)

High-energy storage system

Featured Article - February 2009
Despite the cellular importance of inorganic polyphosphate, particularly in bacteria, exactly how it is processed is not known. Two new polyphosphate kinase structures should make things clearer.Proc Natl Acad Sci USA 105, 17730-17735 (2008)

Transporter mechanism in sight

Featured Article - February 2009
Structural studies of the leucine transporter reveal details of the early steps in substrate transport across the membrane.Science 322, 1655-1661 (2008)

Scavenger Decapping Enzyme DcpS

Featured System - November 2008
Messenger RNA molecules are temporary molecules.

Blocking AmtB

Featured Article - September 2008
Proc Natl Acad Sci USA 104, 42-47 (2007)
Structural Biology Knowledgebase ISSN: 1758-1338
Funded by a grant from the National Institute of General Medical Sciences of the National Institutes of Health