Structural Biology Symposium

IUCr Newsletter (1998). 6(3), 16.

At the Sealy Center in Galveston, Texas, Interactions of viral proteins and nucleic acids related to infectivity, the dynamics of enzyme regulation and folding, and differing approaches to protein design were the main topics at a Structural Biology Symposium that attracted 240 researchers. W.A. Hendrickson (Columbia U., NY) described a complex of the HIV envelope glycoprotein gpl20 with a neutralizing antibody fragment and the D1/D2 domains of CD4, and revealed variable regions of the protein and the added glycosylation that mask many potential antigenic sites, thus serving to hide the functional parts of HIV from the immune system. M. Rossmann showed how the antiviral compound WIN 54954 displaces the mysterious "pocket factor" of the common cold causing human rhinoviruses, thus altering the structure enough to interfere with virus binding or capsid disruption. M. Summers (U. of Maryland) used NMR studies to correlate the crystal structure of the HIV-1 nucleocapsid protein with its structure when bound to HIV-1 RNA. Films of the structure of virus capsids deduced solely from electron microscopy data by E. Chiu included a 9 Å resolution 3D-images of unstained Herpes simplex B capsids at -170°C. M. Hecht (Princeton, NJ) has designed combinatorial libraries based on the periodicity patterns of amino acids in stable protein structure elements. By inserting these elements into appropriate loop structures, one can design a protein having the desired secondary and tertiary elements. H.W. Hellinga (Duke U. Med. Ctr, Durham NC) uses a rational approach to design proteins containing active metal ion centers, metal enzymes. Homme's work illustrated the fact that many effects of point mutations cannot be rationally predicted a priori. M. Schiffer (Argonne Nat'l Lab, Illinois) showed that change of a single amino acid in an immunoglobulin light chain resulted in a "flipped" dimeric structure with more buried surface area and hydrogen bonds than the parent molecule but none of the interactions that stabilized the initial dimer. Working with cytochrome c, M.M. Pierce and B. Hall (UTHSC, San Antonio) suggests that some mutations affect the compactness of the denatured state and that amino acids other than histidine can coordinate the heme prosthetic group. S.S. Taylor (U. of California) presented the structure of c-AMP-Dependent Protein Kinase (APK) and its affectors. The kinase kinetics are directly influenced by the viscosity of the solvent, effects which are at least partly attributable to the need for dynamic motion of the C-helix during catalysis. J. Kuriyan (The Rockefeller U., NY) suggested that movement is particularly important for catalysis in APK as the nucleotide binding site is relatively inaccessible. Such movement may be less necessary within the Src-family tyrosine kinases, which according to his structures have a relatively exposed site for binding GDP.

C.H. Schein
From the ACA Newsletter, Summer 1998