October 2005 issue
Cover illustration: A ribbon diagram of the Kelch domain of human Keap1 showing the conserved water molecules found in each blade of the -propeller (p. 1335).
The crystal structure of the human transthyretin–tetraiodothyroacetic acid complex was determined. The ligand is in an unusual position, penetrating the dimer–dimer interface and interacting with three TTR monomers simultaneously.
The ternary complex structures of C. neoformans TS and human TS are highly conserved. A 1,8-naphthalein derivative that selectively inhibits C. neoformans and E. coli TSs over human TS binds to an open conformation of E. coli TS. Disorder of the inhibitor-binding site in the human apoenzyme may explain the inhibitor specificity.
Use of 1.35 Å SAD data for de novo structure determination of the Kelch domain and for refinement at atomic resolution is described.
The crystal structure of a hypothetical protein (MPN555) from M. pneumoniae revealed a trilobal molecule with at least one central binding pocket or channel. The molecule has structural homology with two bacterial chaperone proteins, which suggests a similar chaperone function for MPN555.
The high-resolution X-ray crystal structures of two anticancer minor-groove-binding quinolinium quaternary salts complexed with the dodecamer d(CGCGAATTCGCG)2 are reported.
Use of the medial axis for automated crystallographic model building is described.
The work of the Israel Structural Proteomics Center (ISPC) to determine the structures of proteins related to human health in their functional context is described.
The absolute configuration of haem A, the prosthetic group of cytochrome c oxidase, was determined to be S by analyzing bond angles.
A medium-throughput strategy has been developed for academic structural biology that meets the twin goals of research output and graduate-student development. The platform incorporates Gateway cloning and 96-well methods for solubility screening and crystallization.
The NNA7 Fab antibody fragment recognizes the human N blood-group antigen, whereas the NNA7-G91S mutant exhibits reduced antigen binding. To provide insight into how these Fab fragments recognize this clinically relevant glycopeptide antigen, the crystal structures of both Fab fragments were solved. The results provide a model for peptide and sugar recognition based upon crystallographic contacts, as well as a bound 2-(N-morpholino)ethanesulfonic acid (MES) molecule trapped in the antigen-combining site.
The crystal structure of fumarase C has been solved in the absence of inhibitors and substrate analogues. This novel crystal structure reports a pH-sensitive shift at the allosteric B site and preservation of the architecture surrounding the conserved active-site water.
Purified Sesbania mosaic virus coat-protein particles have been crystallized and X-ray crystal structures of their mutant capsids have been determined.
The role of water molecules in the Sesbania mosaic virus structure has been analyzed.
Perdeuterated human aldose reductase neutron diffraction data at 2.2 Å resolution was collected from a 0.15 mm3 crystal. Deuterium atoms were clearly seen in the neutron-scattering density map.
The crystallizability of coagulation factor XI has been improved by surface-residue mutation, generating a quadruple mutant that crystallizes easily in the presence of benzamidine and has facilitated the iterative process of structure-based design of factor XI selective inhibitors.
A strategy for crystallization screening using nanolitre drops and a combination of a sparse-matrix screen (JCSG+) and a novel systematic screen (PACT) is presented and discussed.
A historical perspective of the steps leading to the current robot technology available for crystal mounting and data collection is presented. The implications for the future of the field are briefly discussed.