June 2006 issue
This article reviews the issues, methods and strategies involved in obtaining the crystals of protein-ligand complexes that are critical for structure-aided drug design.
A high-resolution structure determination shows that (+)-epi-biotin and (+)-biotin bind similarly to streptavidin by using conformational changes in their tetrahydrothiophene rings to accommodate their different configurations at the C2 carbon.
The crystal structure of human dual-specificity protein tyrosine phosphatase 18 provides the structural basis for the unusual catalytic activity at high temperature.
The structures of the PDI-related protein Wind and three mutants show the same mode of dimerization and only subtle differences in the putative Pipe-binding region, although two of the mutants completely abrogate Pipe transport.
This paper describes the production and structural characterization of the allergen Ves v 2 from wasp venom. Implications for cross-reactivity are discussed.
A survey of crystallization conditions was carried out for all known protein–protein complexes to define the boundaries of their configuration space. Based on the survey, a probability-based sparse-matrix screen and a systematic buffer and pH screen are proposed to facilitate the crystallization of protein–protein complexes.
Various binary complex structures of E. coli malonyl-CoA–acyl carrier protein transacylase are presented, including that of the natural substrate malonyl-CoA. Based on the presented structural data, a possible new catalytic enzyme mechanism is discussed.
The structure of a complex of M. tuberculosis pantothenate kinase with a coenzyme A derivative has been determined in two crystal forms, each at two temperatures. The structure and a comparative analysis involving the known structure of the E. coli enzyme and the sequences of the enzyme from other bacteria show a strong correlation among structural plasticity, evolutionary relatedness and function.
Intermolecular interaction energies between fragments of glycopeptide antibiotics and small peptide ligands are evaluated using X-ray geometries and new methods, suitable for application to very large molecular complexes. The calculation of the electrostatic contributions is based on charge densities constructed with a databank of transferable aspherical atoms, whereas non-electrostatic contributions are evaluated with a new set of atom–atom potentials fitted to symmetry-adapted perturbation-theory results.
Upon introduction of an X-ray pseudo-energy derived from the electron density present at a specific protein residue, protein design algorithms can be used readily for crystallographic model building and refinement purposes.
The structure of the plant invertase inhibitor Nt-CIF from tobacco has been determined in six independent crystal forms covering pH 4.6–9.5.
The high-resolution structure of a new crystal form of human cytoglobin has been determined, revealing an additional helix in the N-terminus and a new dimeric arrangement.
Revisions are based on structures now in the Protein Data Bank with resolution ≤1.25 Å, as well as small-molecule structures in the Cambridge Structural Database; patterns shown in bidentate carboxylates are explored.
The crystal structure of LeACX1 from tomato was determined to 2.74 Å resolution. The packing arrangement observed was unusual, containing three monomers in the asymmetric unit: the biological dimer plus a half dimer.