Wladek Minor, PhD, and his research team at the University of Virginia Health System are celebrating the attainment of an important milestone by the Midwest Center for Structural Genomics (MCSG), an international scientific consortium of which they are part. MCSG, which has been using the genetic code of dangerous human pathogens and other organisms to determine the arrangement of atoms of proteins since 2000, today deposited the three-dimensional structure of its thousandth protein in the Protein Data Bank (PDB), an international database of protein structures that can be accessed by researchers from around the world.
MCSG researchers produce highly purified proteins, crystallize them and then determine their three-dimensional structures using X-ray crystallography. So far, the consortium’s findings have shed light on the origins of anthrax and other disease-causing bacteria such as meningitis, salmonella, cholera and staph. MCSG has also supported the development of treatments for the H1N1 virus by characterizing a key protein nicknamed the “dragon” because of its resemblance to a monstrous dragon’s head.
According to Minor, who is professor of Molecular Physiology and Biological Physics at UVA, his team has contributed both structures and methodologies to the MCSG. “We directly solved many of the protein structures for the MCSG,” Minor notes. “These include the three-dimensional structures of RNase-T (the PSI Featured Molecule of July 2008), the 5′-deoxyribonucleotidase YfbR, a redox-enzyme maturation protein, and the transcriptional regulator TM1030.”
UVA researchers also determined many structures from pathogenic organisms like Vibrio cholera , Staphyloccocus aureus , Helicobacter pylori, Chlamydia trachomatis and Pseudomonas aeurigonosa. The structures have provided important insights into the molecular mechanisms of action of these pathogens, Minor said.
In addition to supporting the work of the MCSG, the methodologies developed at UVA have had a great impact on biomedical science across the world. “Our paper describing the HKL and HKL-2000 programs, which are used to reduce X-ray diffraction data, is cited by over 18,000 scientific papers,” Minor says. “More than 800 recent protein structure deposits to the PDB report the use of the newly developed HKL-3000 program.”
Minor’s laboratory has also developed completely new technologies, including databases to track and analyze molecular biology laboratory experiments and to study protein-protein interactions of structures in the PDB. Some of these technologies have been made available to the wider scientific community through technology transfer and commercialization.
For his achievements, Prof. Wladek Minor received the Virginia Patent Foundation’s Edlich-Henderson Inventor of the Year award in 2007. Several members of his group have registered inventions with the Patent Foundation (Matthew Zimmerman, Marcin Cymborowski, Maksymilian Chruszcz, and Heping Zheng). His group collaborates closely with that of Prof. Zbyszek Otwinowski at the University of Texas Southwestern Medical Center, as well as other members of the MCSG consortium, including Andrzej Joachimiak, Aled Edwards, Alexei Savchenko, and Wayne Anderson.
The MCSG is led by Dr. Andrzej Joachimiak at the U.S. Department of Energy’s (DOE) Argonne National Laboratory. Besides UVA, consortium affiliates include Northwestern University, University of Texas SWMC, Washington University, University of Toronto, University College London and the European Bioinformatics Institute. The MCSG is one of four large-scale NIH centers funded by the Protein Structure Initiative (PSI). The MCSG is the first PSI center to determine the three-dimensional structures of 1000 proteins.
The MCSG’s work continues. As Minor observes, “The avalanche of structures coming from MCSG will improve our understanding of the molecular foundation of human diseases.”