Impacts Range from Fundamental Biology to Disease
Molecular functions go according to form as 3-D structures do life's work
January 21, 2004
Notes to editors and news directors: The Protein Data Bank, a publicly accessible collection of nearly 24,000 macromolecules, is administered by the Research Collaboratory for Structural Bioinformatics with support from the National Science Foundation and seven other federal agencies. A detailed news release announces a new five-year agreement with the RCSB.
Molecule images are available here: http://www.nsf.gov/od/lpa/news/04/pr0408_images.htm.
For additional images, contact the Protein Data Bank by email at firstname.lastname@example.org or visit its web site at www.pdb.org.
Each with its role in a biological process, and many with several roles, every structure in the Protein Data Bank has value. The structures range from small pieces of protein or DNA to complex machines, such as the ribosome.
Among the most intricate and remarkable of nature's machines, the ribosome's structure includes more than 100,000 atoms, reflecting its complex and crucial function as the cell's protein-assembly factory.
A complex cell can have many thousands of different types of protein, each of which is a long chain of amino acids assembled according to the precise instructions found in the DNA sequence of a gene. To use these instructions, the cell first makes a copy of the DNA information in the form of another molecule, a single-stranded kin to DNA called messenger RNA (mRNA).
The mRNA is then threaded through the ribosome, which reads the instructions one step at a time, adding each amino acid in the exact order prescribed by the gene sequence. The result is a specific protein molecule with the precise shape and chemical properties that allow it to provide an important function for the cell. This stepwise process for converting information stored in DNA into functional, biological molecules is referred to as 'gene expression.'
Also represented in the Protein Data Bank's database are enzymes, viruses and molecular assemblies (such as the nucleosome). Their structures provide insight into these molecules' roles in fundamental biological processes and, in some cases, into their possible roles in disease or drug interactions.
The diversity and complexity of the collection is illustrated by those structures highlighted in the PDB's "Molecule of the Month" series, authored by David S. Goodsell of The Scripps Institute of Oceanography (http://www.rcsb.org/pdb/molecules/molecule_list.html).
Examples taken from "Molecule of the Month" follow (with their PDB data ID and a link to profiles).
Viruses (2PLV, 4RHV, 1BBT) http://www.rcsb.org/pdb/molecules/pdb20_1.html
Antibodies (1IGT) http://www.rcsb.org/pdb/molecules/pdb21_1.html
Ribosome (1FJG for the small subunit and 1FFK for the large subunit) http://www.rcsb.org/pdb/molecules/pdb10_1.html
Nucleosome (1AOI) http://www.rcsb.org/pdb/molecules/pdb7_1.html
Green Fluorescent Protein (1GFL) http://www.rcsb.org/pdb/molecules/pdb42_1.html
Additional examples follow to illustrate the breadth of impact of the structural information contained in the Protein Data Bank:
Photosynthesis: The structures of the last of the 3 major assemblies involved in photosynthesis has now been determined revealing for the first time exactly how plants and some bacteria harness sunlight to produce energy for growth. (1JB0, 1IZL, 1UM3)
Breath of Life: Carbonic anhydrase enzymes are essential to a remarkable spectrum of biological processes, ranging from breathing in animals to photosynthesis in plants. The functions performed by these enzymes are so crucial that they may have been invented by nature 3 or more separate times in the course of evolution. (See 1CA2, 1DDZ, 1THJ for examples; also http://www.rcsb.org/pdb/molecules/pdb49_1.html.)
An RNA World: Catalysis - directing a chemical reaction - once thought to be the province of proteins alone is now known to be a property of RNAs, which may have preceded proteins in early evolution. (See 488D for an example.)
Channel Surfing: The structures of channels that control the entry and exit of water and ions from cells reveal how cells control their internal environment. Research on cell membrane channels was recognized by the 2003 Nobel Prize in Chemistry. (1FQY, 1BL8)
HIV (Human Immunodeficiency Virus): Structures such as reverse transcriptase and HIV protease have already been used to develop new drugs used in the fight against AIDS. (7HVP, 1HSG, 1HXB, 1HXW)
Mad Cow disease: The structure of segments of the prion protein (that may form the infectious agent for this disease) has been solved. An understanding of its conversion from normal to the abnormal disease-causing form will help scientists understand the progression of the disease. (1DX0, 1E1W, 1G6W)
SARS (Severe Acute Respiratory Syndrome): The structures of the protease and polymerase proteins of this virus have been used to design drugs against this virus. (1Q2W, 1UK4)
Structure of a portion of the bovine prion protein, a molecule associated with mad cow disease.
Credit and Larger Version
Structure of the largest of the two subunits of the ribosome the 'protein factory' of the cell.
Credit and Larger Version
Sean Kearns, NSF, (703) 292-7963, email: email@example.com
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