The arrangement of identical molecular components can make a dramatic difference. For example, carbon atoms can be arranged into dull graphite (left) or sparkly diamonds (right). See image 2506 for an illustration without examples.

This image is a computer-generated model of the approximately 4.2 million atoms of the HIV capsid, the shell that contains the virus' genetic material. Scientists determined the exact structure of the capsid and the proteins that it's made of using a variety of imaging techniques and analyses. They then entered these data into a supercomputer that produced the atomic-level image of the capsid. This structural information could be used for developing drugs that target the capsid, possibly leading to more effective therapies. Related to image 6601.

This illustration highlights spherical pre-synaptic vesicles that carry the neurotransmitter glutamate. The presynaptic and postsynaptic membranes are shown with proteins relevant for transmitting and modulating the neuronal signal.

PDB 101’s Opioids and Pain Signaling video explains how glutamatergic synapses are involved in the process of pain signaling.

Glucose (top) and sucrose (bottom) are sugars made of carbon, hydrogen, and oxygen atoms. Carbohydrates include simple sugars like these and are the main source of energy for the human body.

T cells are white blood cells that are important in defending the body against bacteria, viruses and other pathogens. Each T cell carries proteins, called T-cell receptors, on its surface that are activated when they come in contact with an invader. This activation sets in motion a cascade of biochemical changes inside the T cell to mount a defense against the invasion. Scientists have been interested for some time what happens after a T-cell receptor is activated. One obstacle has been to study how this signaling cascade, or pathway, proceeds inside T cells.

In this image, researchers have created a T-cell receptor pathway consisting of 12 proteins outside the cell on an artificial membrane. The image shows two key steps during the signaling process: clustering of a protein called linker for activation of T cells (LAT) (blue) and polymerization of the cytoskeleton protein actin (red). The findings show that the T-cell receptor signaling proteins self-organize into separate physical and biochemical compartments. This new system of studying molecular pathways outside the cells will enable scientists to better understand how the immune system combats microbes or other agents that cause infection.

To learn more how researchers assembled this T-cell receptor pathway, see this press release from HHMI's Marine Biological Laboratory Whitman Center. Related to video 3786.

Dose-response curves determine how much of a drug (X-axis) causes a particular effect, or a side effect, in the body (Y-axis). Featured in Medicines By Design.

A model of the molecule himastatin, which was first isolated from the bacterium Streptomyces himastatinicus. Himastatin shows antibiotic activity. The researchers who created this image developed a new, more concise way to synthesize himastatin so it can be studied more easily.

More information about the research that produced this image can be found in the Science paper “Total synthesis of himastatin” by D’Angelo et al.

Related to image 6850 and video 6851.

Active site of E. coli response regulator PhoB.

An image of the area of the mouse brain that serves as the 'master clock,' which houses the brain's time-keeping neurons. The nuclei of the clock cells are shown in blue. A small molecule called VIP, shown in green, enables neurons in the central clock in the mammalian brain to synchronize.

In 2007, the FDA modified warfarin's label to indicate that genetic makeup may affect patient response to the drug. The widely used blood thinner is sold under the brand name Coumadin®. Scientists involved in the NIH Pharmacogenetics Research Network are investigating whether genetic information can be used to improve optimal dosage prediction for patients.

CCD-1 is an enzyme produced by the bacterium Clostridioides difficile that helps it resist antibiotics. Using X-ray crystallography, researchers determined the structure of a complex between CCD-1 and the antibiotic cefotaxime (purple, yellow, and blue molecule). The structure revealed that CCD-1 provides extensive hydrogen bonding (shown as dotted lines) and stabilization of the antibiotic in the active site, leading to efficient degradation of the antibiotic.

Related to images 6764, 6765, and 6766.

CCD-1 is an enzyme produced by the bacterium Clostridioides difficile that helps it resist antibiotics. Researchers crystallized complexes where a CCD-1 molecule and a molecule of the antibiotic cefotaxime were bound together. Then, they shot X-rays at the complexes to determine their structure—a process known as X-ray crystallography. This image shows the X-ray diffraction pattern of a complex.

Related to images 6764, 6766, and 6767.

Drugs enter different layers of skin via intramuscular, subcutaneous, or transdermal delivery methods. See image 2532 for a labeled version of this illustration. Featured in Medicines By Design.

Ecteinascidin 743 (ET-743, brand name Yondelis), was discovered and isolated from a sea squirt, Ecteinascidia turbinata, by NIGMS grantee Kenneth Rinehart at the University of Illinois. It was synthesized by NIGMS grantees E.J. Corey and later by Samuel Danishefsky. Multiple versions of this structure are available as entries 2790-2797.

Ecteinascidin 743 (ET-743, brand name Yondelis), was discovered and isolated from a sea squirt, Ecteinascidia turbinata, by NIGMS grantee Kenneth Rinehart at the University of Illinois. It was synthesized by NIGMS grantees E.J. Corey and later by Samuel Danishefsky. Multiple versions of this structure are available as entries 2790-2797.

Acetylsalicylate (bottom) is the aspirin of today. Adding a chemical tag called an acetyl group (shaded box, bottom) to a molecule derived from willow bark (salicylate, top) makes the molecule less acidic (and easier on the lining of the digestive tract), but still effective at relieving pain. See image 2529 for an unlabeled version of this illustration. Featured in Medicines By Design.

The enzyme CCP is found in the mitochondria of baker’s yeast. Scientists study the chemical reactions that CCP triggers, which involve a water molecule, iron, and oxygen. This structure was determined using an X-ray free electron laser.

This network map shows the overlap (green) between the long QT syndrome (yellow) and epilepsy (blue) protein-interaction neighborhoods located within the human interactome. Researchers have learned to integrate genetic, cellular and clinical information to find out why certain medicines can trigger fatal heart arrhythmias. Featured in Computing Life magazine.

Antibiotic resistance in microbes is a serious health concern. So researchers have turned their attention to how bacteria undo the action of some antibiotics. Here, scientists set out to find the conditions that help individual bacterial cells survive in the presence of the antibiotic rifampicin. The research team used Mycobacterium smegmatis, a more harmless relative of Mycobacterium tuberculosis, which infects the lung and other organs to cause serious disease.

In this video, genetically identical mycobacteria are growing in a miniature growth chamber called a microfluidic chamber. Using live imaging, the researchers found that individual mycobacteria will respond differently to the antibiotic, depending on the growth stage and other timing factors. The researchers used genetic tagging with green fluorescent protein to distinguish cells that can resist rifampicin and those that cannot. With this gene tag, cells tolerant of the antibiotic light up in green and those that are susceptible in violet, enabling the team to monitor the cells' responses in real time.

To learn more about how the researchers studied antibiotic resistance in mycobacteria, see this news release from Tufts University. Related to image 5751.

CCD-1 is an enzyme produced by the bacterium Clostridioides difficile that helps it resist antibiotics. Using X-ray crystallography, researchers determined the structure of a CCD-1 molecule and a molecule of the antibiotic cefotaxime bound together. The structure revealed that CCD-1 provides extensive hydrogen bonding and stabilization of the antibiotic in the active site, leading to efficient degradation of the antibiotic.

Related to images 6764, 6765, and 6767.

Acetylsalicylate (bottom) is the aspirin of today. Adding a chemical tag called an acetyl group (shaded box, bottom) to a molecule derived from willow bark (salicylate, top) makes the molecule less acidic (and easier on the lining of the digestive tract), but still effective at relieving pain. See image 2530 for a labeled version of this illustration. Featured in Medicines By Design.

T cells are white blood cells that are important in defending the body against bacteria, viruses and other pathogens. Each T cell carries proteins, called T-cell receptors, on its surface that are activated when they come in contact with an invader. This activation sets in motion a cascade of biochemical changes inside the T cell to mount a defense against the invasion. Scientists have been interested for some time what happens after a T-cell receptor is activated. One obstacle has been to study how this signaling cascade, or pathway, proceeds inside T cells.

In this video, researchers have created a T-cell receptor pathway consisting of 12 proteins outside the cell on an artificial membrane. The video shows three key steps during the signaling process: phosphorylation of the T-cell receptor (green), clustering of a protein called linker for activation of T cells (LAT) (blue) and polymerization of the cytoskeleton protein actin (red). The findings show that the T-cell receptor signaling proteins self-organize into separate physical and biochemical compartments. This new system of studying molecular pathways outside the cells will enable scientists to better understand how the immune system combats microbes or other agents that cause infection.

To learn more how researchers assembled this T-cell receptor pathway, see this press release from HHMI's Marine Biological Laboratory Whitman Center. Related to image 3787.

A protein called kinesin (blue) is in charge of moving cargo around inside cells and helping them divide. It's powered by biological fuel called ATP (bright yellow) as it scoots along tube-like cellular tracks called microtubules (gray).

Shiga toxin (green) is sorted from the endosome into membrane tubules (red), which then pinch off and move to the Golgi apparatus.

Zinc is required for the function of more than 300 enzymes, including those that help regulate gene expression, in various organisms including humans. Researchers study how plants acquire, sequester and distribute zinc to find ways to increase the zinc content of crops to improve human health. Using synchrotron X-ray fluorescence technology, they created this heat map of zinc levels in an Arabidopsis thaliana plant leaf. This image is a winner of the 2015 FASEB Bioart contest and was featured in the NIH Director's blog.

A representation of a patient’s brain waves after receiving the anesthetic propofol. All anesthetics create brain wave changes that vary depending on the patient’s age and the type and dose of anesthetic used. These changes are visible in raw electroencephalogram (EEG) readings, but they’re easier to interpret using a spectrogram where the signals are broken down by time (x-axis), frequency (y-axis), and power (color scale). This spectrogram shows the changes in brain waves before, during, and after propofol-induced anesthesia. The patient is unconscious from minute 5, upon propofol administration, through minute 69 (change in power and frequency). But, between minutes 35 and 48, the patient fell into a profound state of unconsciousness (disappearance of dark red oscillations between 8 to 12 Hz), which required the anesthesiologist to adjust the rate of propofol administration. The propofol was stopped at minute 62 and the patient woke up around minute 69.

Luciferase-based imaging enables visualization and quantification of internal organs and transplanted cells in live adult zebrafish. In this image, a cardiac muscle-restricted promoter drives firefly luciferase expression.
For imagery of both the lateral and overhead view go to 3556.
For imagery of the lateral view go to 3558.
For more information about the illumated area go to 3559.

Circadian rhythms are physical, mental, and behavioral changes that follow a 24-hour cycle. Circadian rhythms are influenced by light and regulated by the brain’s suprachiasmatic nucleus (SCN), sometimes referred to as a master clock. Learn more in NIGMS’ circadian rhythms fact sheet. See 6614 for the Spanish version of this infographic.

Ecteinascidin 743 (ET-743, brand name Yondelis), was discovered and isolated from a sea squirt, Ecteinascidia turbinata, by NIGMS grantee Kenneth Rinehart at the University of Illinois. It was synthesized by NIGMS grantees E.J. Corey and later by Samuel Danishefsky. Multiple versions of this structure are available as entries 2790-2797.

X-ray co-crystal structure of Src kinase bound to a DNA-templated macrocycle inhibitor. Related to images 3413, 3414, 3415, 3416, 3417, and 3419.

This image shows the structure of the CYP17A1 enzyme (ribbons colored from blue N-terminus to red C-terminus), with the associated heme colored black. The prostate cancer drug abiraterone is colored gray. Cytochrome P450 enzymes bind to and metabolize a variety of chemicals, including drugs. Cytochrome P450 17A1 also helps create steroid hormones. Emily Scott's lab is studying how CYP17A1 could be selectively inhibited to treat prostate cancer. She and graduate student Natasha DeVore elucidated the structure shown using X-ray crystallography. Dr. Scott created the image (both white bg and transparent bg) for the NIGMS image gallery. See the "Medium-Resolution Image" for a PNG version of the image that is transparent.

The nucleolus is a small but very important protein complex located in the cell's nucleus. It forms on the chromosomes at the location where the genes for the RNAs are that make up the structure of the ribosome, the indispensable cellular machine that makes proteins from messenger RNAs.

However, how the nucleolus grows and maintains its structure has puzzled scientists for some time. It turns out that even though it looks like a simple liquid blob, it's rather well-organized, consisting of three distinct layers: the fibrillar center, where the RNA polymerase is active; the dense fibrillar component, which is enriched in the protein fibrillarin; and the granular component, which contains a protein called nucleophosmin. Researchers have now discovered that this multilayer structure of the nucleolus arises from difference in how the proteins in each compartment mix with water and with each other. These differences let them readily separate from each other into the three nucleolus compartments.

This video of nucleoli in the eggs of a commonly used lab animal, the frog Xenopus laevis, shows how each of the compartments (the granular component is shown in red, the fibrillarin in yellow-green, and the fibrillar center in blue) spontaneously fuse with each other on encounter without mixing with the other compartments. For more details on this research, see this press release from Princeton. Related to video 3791, image 3792 and image 3793.

Ecteinascidin 743 (ET-743, brand name Yondelis), was discovered and isolated from a sea squirt, Ecteinascidia turbinata, by NIGMS grantee Kenneth Rinehart at the University of Illinois. It was synthesized by NIGMS grantees E.J. Corey and later by Samuel Danishefsky. Multiple versions of this structure are available as entries 2790-2797.

The TRPA1 protein is responsible for the burn you feel when you taste a bite of sushi topped with wasabi. Known therefore informally as the "wasabi receptor," this protein forms pores in the membranes of nerve cells that sense tastes or odors. Pungent chemicals like wasabi or mustard oil cause the pores to open, which then triggers a tingling or burn on our tongue. This receptor also produces feelings of pain in response to chemicals produced within our own bodies when our tissues are damaged or inflamed. Researchers used cryo-EM to reveal the structure of the wasabi receptor at a resolution of about 4 angstroms (a credit card is about 8 million angstroms thick). This detailed structure can help scientists understand both how we feel pain and how we can limit it by developing therapies to block the receptor. For more on cryo-EM see the blog post Cryo-Electron Microscopy Reveals Molecules in Ever Greater Detail.

X-ray co-crystal structure of Src kinase bound to a DNA-templated macrocycle inhibitor. Related to 3413, 3414, 3416, 3417, 3418, and 3419.

A red poppy.

A white poppy. View cropped image of a poppy here 3423.

X-ray co-crystal structure of Src kinase bound to a DNA-templated macrocycle inhibitor. Related to 3413, 3414, 3415, 3417, 3418, and 3419.

Luciferase-based imaging enables visualization and quantification of internal organs and transplanted cells in live adult zebrafish. This image shows how luciferase-based imaging could be used to visualize the heart for regeneration studies (left), or label all tissues for stem cell transplantation (right).
For imagery of both the lateral and overhead view go to 3556.
For imagery of the overhead view go to 3557.
For imagery of the lateral view go to 3558.

Drosophila adult brain showing that an adipokine (fat hormone) generates a response from neurons (aqua) and regulates insulin-producing neurons (red).

Related to images 6982, 6983, and 6984.

Luciferase-based imaging enables visualization and quantification of internal organs and transplanted cells in live adult zebrafish. In this image, a cardiac muscle-restricted promoter drives firefly luciferase expression. This is the lateral and overhead (Bottom) view.
For imagery of the overhead view go to 3557.
For imagery of the lateral view go to 3558.
For more information about the illumated area go to 3559.

These yeast cells were exposed to a glucose (sugar) shortage. This caused the cells to compartmentalize HMGCR (green)—an enzyme involved in making cholesterol—to a patch on the nuclear envelope next to the vacuole/lysosome (purple). This process enhanced HMGCR activity and helped the yeast adapt to the glucose shortage. Researchers hope that understanding how yeast regulate cholesterol could ultimately lead to new ways to treat high cholesterol in people. This image was captured using a fluorescence microscope.

X-ray co-crystal structure of Src kinase bound to a DNA-templated macrocycle inhibitor. Related to 3414, 3415, 3416, 3417, 3418, and 3419.

The plasma membrane is a cell's protective barrier. See image 2524 for a labeled version of this illustration. Featured in The Chemistry of Health.

PETase enzyme degrades polyester plastic (polyethylene terephthalate, or PET) into monohydroxyethyl terephthalate (MHET). Then, MHETase enzyme degrades MHET into its constituents ethylene glycol (EG) and terephthalic acid (TPA).

Find these in the RCSB Protein Data Bank: PET hydrolase (PDB entry 5XH3) and MHETase (PDB entry 6QGA).

To simulate the consequences of disrupting bacterial cell-to-cell communication, called quorum sensing, in the crypts (small chambers within the colon), the researchers experimented with an inhibitor molecule (i.e., antagonist) to turn off quorum sensing in methicillin-resistant Staphylococcus aureus (MRSA), an antibiotic-resistant strain of bacteria that often causes human infections. In this experiment, a medium promoting bacterial growth flows through experimental chambers mimicking the colon environment. The chambers on the right contained no antagonist. In the left chambers, after being added to the flowing medium, the quorum-sensing-inhibiting molecules quickly spread throughout the crevices, inactivating quorum sensing and reducing colonization. These results suggest a potential strategy for addressing MRSA virulence via inhibitors of bacterial communication. You can read more about this research here.

This 1 1/2-minute video animation was produced for chemical biologist Stuart Schreiber's lab page. The animation shows how diverse chemical structures can be produced in the lab.

The nucleolus is a small but very important protein complex located in the cell's nucleus. It forms on the chromosomes at the location where the genes for the RNAs are that make up the structure of the ribosome, the indispensable cellular machine that makes proteins from messenger RNAs.

However, how the nucleolus grows and maintains its structure has puzzled scientists for some time. It turns out that even though it looks like a simple liquid blob, it's rather well-organized, consisting of three distinct layers: the fibrillar center, where the RNA polymerase is active; the dense fibrillar component, which is enriched in the protein fibrillarin; and the granular component, which contains a protein called nucleophosmin. Researchers have now discovered that this multilayer structure of the nucleolus arises from differences in how the proteins in each compartment mix with water and with each other. These differences let the proteins readily separate from each other into the three nucleolus compartments.

This video of nucleoli in the eggs of a commonly used lab animal, the frog Xenopus laevis, shows how each of the compartments (the granular component is shown in red, the fibrillarin in yellow-green, and the fibrillar center in blue) spontaneously fuse with each other on encounter without mixing with the other compartments.

For more details on this research, see this press release from Princeton. Related to video 3789, image 3792 and image 3793.

Ecteinascidin 743 (ET-743, brand name Yondelis), was discovered and isolated from a sea squirt, Ecteinascidia turbinata, by NIGMS grantee Kenneth Rinehart at the University of Illinois. It was synthesized by NIGMS grantees E.J. Corey and later by Samuel Danishefsky. Multiple versions of this structure are available as entries 2790-2797.

Colonies of bacteria growing despite high concentrations of antibiotics. These colonies are visible both by eye, as seen on the left, and by bioluminescence imaging, as seen on the right. The bioluminescent color indicates the metabolic activity of these bacteria, with their red centers indicating high metabolism.

More information about the research that produced this image can be found in the Antimicrobial Agents and Chemotherapy paper “Novel aminoglycoside-tolerant phoenix colony variants of Pseudomonas aeruginosa” by Sindeldecker et al.