SEARCH

SEARCH BY CITATION

1587 Creating a community resource for protein science

  1. Top of page
  2. 1587 Creating a community resource for protein science
  3. 1620 Structural basis for proton conduction and inhibition by the influenza M2 protein
  4. 1597 The enzymes of biotin dependent CO2 metabolism: What structures reveal about their reaction mechanisms

Helen M. Berman

Established in 1971, the Protein Data Bank (PDB) archive has served as a community resource for protein science. Since that time, marked changes and advances in technologies and methods used for structure determination have produced the more than 84,000 entries currently available in the PDB. This article describes how the management, data content, infrastructure, and community have influenced the continued development of the PDB. It also analyzes the corpus of data to identify trends in the field of structural biology.

1620 Structural basis for proton conduction and inhibition by the influenza M2 protein

  1. Top of page
  2. 1587 Creating a community resource for protein science
  3. 1620 Structural basis for proton conduction and inhibition by the influenza M2 protein
  4. 1597 The enzymes of biotin dependent CO2 metabolism: What structures reveal about their reaction mechanisms

Mei Hong and William F. DeGrado

The influenza M2 protein forms an acid-activated and drug-sensitive proton channel. Biochemical studies of this proton channel are now dovetailed by atomic-resolution structures and dynamics of the protein, much of which determined using solid-state NMR spectroscopy. Protons are conducted through a hydrogen-bonded chain of water and a key histidine residue in the transmembrane domain. The imidazole ring reorients to bind and unbind protons from water on the microsecond timescale. The antiviral drug amantadine binds the pore of the channel near a serine residue, which dehydrates the pore and prevents histidine-mediated proton shuttling. These mechanistic insights are guiding the design of new inhibitors that target drug-resistant M2 variants.

1597 The enzymes of biotin dependent CO2 metabolism: What structures reveal about their reaction mechanisms

  1. Top of page
  2. 1587 Creating a community resource for protein science
  3. 1620 Structural basis for proton conduction and inhibition by the influenza M2 protein
  4. 1597 The enzymes of biotin dependent CO2 metabolism: What structures reveal about their reaction mechanisms

Grover L. Waldrop, Hazel M. Holden, and Martin St. Maurice

Biotin, first discovered in 1936, is a cofactor for a class of enzymes involved in CO2 metabolism. The past 18 years have witnessed an explosion in the number of three-dimensional structures reported for biotin-dependent enzymes. The focus of this review is on the structures of these proteins and on how the information gleaned from X-ray analyses has provided a molecular foundation for understanding their catalytic mechanisms. A thorough understanding of biotin-dependent catalysis is critically important not only from a basic science perspective but also from a translation approach given that some of these enzymes are targets for the development of anti-obesity agents, antibiotics, and herbicides.