A 3-D model of the alkaloid serratezomine A shows the molecule's complex ring structure.

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.

A cropped image of a white poppy. View poppy uncropped here 3424.

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.

The activator cancer cell culture, right, contains a chemical that causes the cells to emit light when in the presence of immune cells.

A drug's life in the body. Medicines taken by mouth pass through the liver before they are absorbed into the bloodstream. Other forms of drug administration bypass the liver, entering the blood directly. See 2528 for a labeled version of this illustration. Featured in Medicines By Design.

Bacillus anthracis (anthrax) cells being killed by a fluorescent trans-translation inhibitor, which disrupts bacterial protein synthesis. The inhibitor is naturally fluorescent and looks blue when it is excited by ultraviolet light in the microscope. This is a black-and-white version of Image 3525.

The molecule on the left is an electrostatic potential map of the van der Waals surface of the transition state for human purine nucleoside phosphorylase. The colors indicate the electron density at any position of the molecule. Red indicates electron-rich regions with negative charge and blue indicates electron-poor regions with positive charge. The molecule on the right is called DADMe-ImmH. It is a chemically stable analogue of the transition state on the left. It binds to the enzyme millions of times tighter than the substrate. This inhibitor is in human clinical trials for treating patients with gout. This image appears in Figure 4, Schramm, V.L. (2011) Annu. Rev. Biochem. 80:703-732.

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

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 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 2507 for an illustration with examples.

This animation shows atoms of the HIV capsid, the shell that encloses the virus's genetic material. Scientists determined the exact structure of the capsid using a variety of imaging techniques and analyses. They then entered this data into a supercomputer to produce this image. Related to image 3477.

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.

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.

Bacillus anthracis (anthrax) cells being killed by a fluorescent trans-translation inhibitor, which disrupts bacterial protein synthesis. The inhibitor is naturally fluorescent and looks blue when it is excited by ultraviolet light in the microscope. This is a color version of Image 3481.

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 3418.

Ionic and covalent bonds hold molecules, like sodium chloride and chlorine gas, together. Hydrogen bonds among molecules, notably involving water, also play an important role in biology. See image 2519 for an unlabeled version of this illustration. Featured in The Chemistry of Health.

Antibodies are among the most promising therapies for certain forms of cancer, but patients must take them intravenously, exposing healthy tissues to the drug and increasing the risk of side effects. A team of biochemists packed the anticancer antibodies into porous silica particles to deliver a heavy dose directly to tumors in mice.

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.

Enzymes speed up chemical reactions by reducing the amount of energy needed for the reactions. The substrate (lactose) binds to the active site of the enzyme (lactase) and is converted into products (sugars).

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.

The signal is obtained by allowing proteins in human serum to interact with glycan (polysaccharide) arrays. The arrays are shown in replicate so the pattern is clear. Each spot contains a specific type of glycan. Proteins have bound to the spots highlighted in green.

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.

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 wreath represents the molecular structure of a protein, Cas4, which is part of a system, known as CRISPR, that bacteria use to protect themselves against viral invaders. The green ribbons show the protein's structure, and the red balls show the location of iron and sulfur molecules important for the protein's function. Scientists harnessed Cas9, a different protein in the bacterial CRISPR system, to create a gene-editing tool known as CRISPR-Cas9. Using this tool, researchers are able to study a range of cellular processes and human diseases more easily, cheaply and precisely. In December, 2015, Science magazine recognized the CRISPR-Cas9 gene-editing tool as the "breakthrough of the year." Read more about Cas4 in the December 2015 Biomedical Beat post A Holiday-Themed Image Collection.

Ionic and covalent bonds hold molecules, like sodium chloride and chlorine gas, together. Hydrogen bonds among molecules, notably involving water, also play an important role in biology. See image 2520 for a labeled version of this illustration. Featured in The Chemistry of Health.

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 (lateral view).
For imagery of both the lateral and overhead view go to 3556.
For imagery of the overhead view go to 3557.
For more information about the illumated area go to 3559.

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.

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.

The world's smallest motor, ATP synthase, generates energy for the cell. See image 2518 for a labeled version of this illustration. Featured in The Chemistry of Health.

This graphic that resembles a firework was created from a picture of a fruit fly spermatid. This fruit fly spermatid recycles various molecules, including malformed or damaged proteins. Actin filaments (red) in the cell draw unwanted proteins toward a barrel-shaped structure called the proteasome (green clusters), which degrades the molecules into their basic parts for re-use.

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.

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 and causes serious disease.

In this image, 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 video 5752.

Adult Drosophila abdominal fat tissue showing cell nuclei labelled in magenta. The upper panel is from well-fed flies, and the lower panel is from flies that have been deprived of food for 4 hours. Starvation results in the accumulation of a key adipokine—a fat hormone (blue-green dots).

Related to images 6982, 6983, and 6985.

A red poppy.

This computer algorithm plots all feasible small carbon-based molecules as though they were cities on a map and identifies huge, unexplored spaces that may help fuel research into new drug therapies. Featured in the May 16, 2013 issue of Biomedical Beat.

Los ritmos circadianos son cambios físicos, mentales y de comportamiento que siguen un ciclo de 24 horas. Los ritmos circadianos se ven influenciados por la luz y están regulados por el núcleo supraquiasmático del cerebro, a veces denominado el reloj principal.

Vea 6613 para la versión en inglés de esta infografía.

Kinases are enzymes that add phosphate groups (red-yellow structures) to proteins (green), assigning the proteins a code. In this reaction, an intermediate molecule called ATP (adenosine triphosphate) donates a phosphate group from itself, becoming ADP (adenosine diphosphate). See image 2535 for a labeled version of this illustration. Featured in Medicines By Design.

The atomic structure of the morphine biosynthetic enzyme salutaridine reductase bound to the cofactor NADPH. The substrate salutaridine is shown entering the active site.

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.

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.

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.

CCD-1 is an enzyme produced by the bacterium Clostridioides difficile that helps it resist antibiotics. Here, researchers crystallized bound pairs of CCD-1 molecules and molecules of the antibiotic cefotaxime. This enabled their structure to be studied using X-ray crystallography.

Related to images 6765, 6766, and 6767.

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.

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.

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.

Fat tissue from the abdomen of a genetically mosaic adult fruit fly. Genetic mosaicism means that the fly has cells with different genotypes even though it formed from a single zygote. This specific mosaicism results in accumulation of a critical fly adipokine (blue-green) within the fat tissue cells that have reduced expression a key nutrient sensing gene (in left panel). The dotted line shows the cells lacking the gene that is present and functioning in the rest of the cells. Nuclei are labelled in magenta. This image was captured using a confocal microscope and shows a maximum intensity projection of many slices.

Related to images 6982, 6984, and 6985.

Recombinant proteins such as the prion protein shown here are often used to model how proteins misfold and sometimes polymerize in neurodegenerative disorders. This prion protein was expressed in E. coli, purified and fibrillized at pH 7. Image taken in 2004 for a research project by Roger Moore, Ph.D., at Rocky Mountain Laboratories that was published in 2007 in Biochemistry. This image was not used in the publication.