We use cookies to understand how you use our site and to improve your experience. This includes personalizing content and advertising. To learn more, click here. By continuing to use our site, you accept our use of cookies. Cookie Policy.

Features Partner Sites Information LinkXpress hp
Sign In
Advertise with Us
PURITAN MEDICAL

Download Mobile App




Drug Developers Turn to Advanced Crystallography Techniques for Critical Structural Information

By LabMedica International staff writers
Posted on 24 Dec 2012
The three-dimensional structure of the enzyme cathepsin B was established within intact cells of the protozoan parasite Trypanosoma brucei by researchers employing an intensely powerful free-electron X-ray laser. More...


T. brucei causes African sleeping sickness, a disease that threatens more than 60 million people in sub-Saharan Africa and annually kills an estimated 30,000 people. Currently no good drug solutions exist for treatment of the disease. The enzyme cathepsin B is among the potential targets for drugs under development. However, methods used so far to study the structure of the mature, active form of cathepsin B have not provided sufficient information for the design of a safe and specific drug against the parasite.

In the current study investigators at Arizona State University (Tempe, USA) and their colleagues at the University of Hamburg (Germany) and the University of Lübeck (Germany) combined two recent innovations, in vivo crystallization and serial femtosecond crystallography, to obtain the room-temperature 0.21 nm (2.1 Angstrom) resolution structure of the fully glycosylated precursor complex of cathepsin B.

To obtain this unprecedented resolution the investigators used the free-electron laser Linac Coherent Light Source (LCLS) at the [US] National Accelerator Laboratory SLAC (Palo Alto, CA, USA). This intensely powerful light source allowed the structure of the enzyme to be determined from one micrometer-sized in vivo crystals. An aqueous suspension of enzyme crystals was passed through the path of the laser beam, which fired approximately 120 times per second. On average, every eleventh shot impacted a crystal, resulting in a total of 293,195 diffraction images being recorded.

This huge number of images could only be processed by massive parallel computing, to first generate a three-dimensional map of all diffracting signals from which an image of the enzyme structure was calculated. The final result, which was published in the November 29, 2012, online edition of the journal Science, revealed the enzyme's structure with a resolution of 0.21 nm.

"These images of an enzyme, which is a drug target for sleeping sickness, are the first results from our new "diffract-then-destroy" snapshot X-ray laser method to show new biological structures which have not been seen before,” said contributing author Dr. John Spence, professor of physics at Arizona State University.

“This paper is so exciting as it is based on nanocrystals grown by the groups at in Hamburg and at the University of Lübeck inside living insect cells,” said contributing author Dr. Petra Fromme, professor of chemistry and biochemistry at Arizona State University. “This is the first novel structure determined by the new method of femtosecond crystallography. The structure may be of great importance for the development of new drugs to fight sleeping sickness, as it shows novel features of the structure of the cathepsin B protein, a protease that is essential for the pathogenesis, including the structure of natural inhibitor peptide bound in the catalytic cleft of the enzyme.”

Related Links:

Arizona State University
University of Hamburg
US National Accelerator Laboratory SLAC



New
Gold Member
Serological Pipets
INTEGRA Serological Pipets
3-Part Differential Hematology Analyzer
Swelab Alfa Plus Sampler
New
HBV DNA Test
GENERIC HBV VIRAL LOAD VER 2.0
New
Gold Member
Hematology Analyzer
Medonic M32B
Read the full article by registering today, it's FREE! It's Free!
Register now for FREE to LabMedica.com and get access to news and events that shape the world of Clinical Laboratory Medicine.
  • Free digital version edition of LabMedica International sent by email on regular basis
  • Free print version of LabMedica International magazine (available only outside USA and Canada).
  • Free and unlimited access to back issues of LabMedica International in digital format
  • Free LabMedica International Newsletter sent every week containing the latest news
  • Free breaking news sent via email
  • Free access to Events Calendar
  • Free access to LinkXpress new product services
  • REGISTRATION IS FREE AND EASY!
Click here to Register








DIASOURCE (A Biovendor Company)

Channels

Molecular Diagnostics

view channel
Image: A diagnostic test can distinguish patients with head and neck squamous cell carcinoma who can be cured with surgery alone (Photo courtesy of University of Turku)

Novel Diagnostic Tool to Revolutionize Treatment Guidance of Head and Neck Cancer

Head and neck squamous cell carcinoma (HNSCC) is a solid tumor type commonly treated with surgery. However, there has been no clinically available method to determine which patients can be cured with surgery... Read more

Hematology

view channel
Image: The microfluidic device for passive separation of platelet-rich plasma from whole blood (Photo courtesy of University of the Basque Country)

Portable and Disposable Device Obtains Platelet-Rich Plasma Without Complex Equipment

Platelet-rich plasma (PRP) plays a crucial role in regenerative medicine due to its ability to accelerate healing and repair tissue. However, obtaining PRP traditionally requires expensive centrifugation... Read more

Immunology

view channel
Image: The 3D paper-based analytical device has shown high clinical accuracy for adult-onset immunodeficiency (Photo courtesy of National Taiwan University)

Paper-Based Device Accurately Detects Immune Defects in 10 Minutes

Patients with hidden immune defects are especially vulnerable to severe and persistent infections, often due to autoantibodies that block interferon-gamma (IFN-γ), a key molecule in immune defense.... Read more

Microbiology

view channel
Image: The groundbreaking salmonella antimicrobial resistance prediction platform has demonstrated 95% accuracy (Photo courtesy of Yujie You et al., DOI: 10.1016/j.eng.2025.01.013)

New Platform Leverages AI and Quantum Computing to Predict Salmonella Antimicrobial Resistance

Antimicrobial-resistant Salmonella strains are a growing public health concern due to the overuse of antimicrobials and the rise of genetic mutations. Accurate prediction of resistance is crucial for effective... Read more

Pathology

view channel
Image: The smart microscope can predict the onset of misfolded protein aggregation, a hallmark of neurodegenerative diseases (Photo courtesy of EPFL)

Self-Driving Microscope Tracks and Analyzes Misfolded Protein Aggregation in Real Time

The accumulation of misfolded proteins in the brain is central to the progression of neurodegenerative diseases like Huntington’s, Alzheimer’s, and Parkinson’s. Yet to the human eye, proteins that are... Read more

Technology

view channel
Image: The Check4 gene-detection platform (Photo courtesy of IdentifySensors)

Electronic Biosensors Used to Detect Pathogens Can Rapidly Detect Cancer Cells

A major challenge in healthcare is the early and affordable detection of serious diseases such as cancer. Early diagnosis remains difficult due to the complexity of identifying specific genetic markers... Read more
Copyright © 2000-2025 Globetech Media. All rights reserved.