Structural analysis of Pneumocystis carinii and human DHFR complexes with NADPH and a series of five potent 6-[5′-(ω-carboxyalk­oxy)benzyl]pyrido[2,3-d]pyrimidine derivatives

These data reveal that the ethyl esters of a series of 5′-(ω-carboxyalkoxy)benzylpyrido[2,3-d]pyrimidines have flexible side-chain conformations that do not optimize interactions with Arg75 in pcDHFR. Also, a novel conformation not reported in other DHFR structures was observed for one conformer of one of the compounds that had a disordered side chain.

Extending the usability of the phasing power of diselenide bonds: SeCys SAD phasing of CsgC using a non-auxotrophic strain

The successful incorporation of SeCys and SeMet into a recombinant protein, yielding derivatized crystals suitable for phasing, is reported. This is the first report of such double derivatization using non-auxotrophic E. coli strains and where SeCys SAD was sufficient for phasing with no contribution from substituted methionine.

The structure of human leucine carboxyl methyltransferase 1 that regulates protein phosphatase PP2A

The crystal structure of a human PP2A methyltransferase enzyme has been determined at 2.0 Å resolution. The structure provides a foundation for the development of specific inhibitors of PP2A methylation, which regulates PP2A holoenzyme assembly.

Exploring binding sites other than the catalytic core in the crystal structure of the catalytic domain of MKP-4

A 2.7 Å resolution crystal structure of the catalytic domain of map kinase phosphatase 4 (MKP-4C) is presented.

Single isomorphous replacement phasing of selenome­thionine-containing proteins using UV-induced radiation damage

Selenomethionine-derivatized protein crystals undergo site-specific ultraviolet laser-induced radiation damage, which was successfully exploited for radiation-damage-induced phasing of X-ray diffraction data.

Multi-crystal anomalous diffraction for low-resolution macromolecular phasing

Anomalous diffraction signals can be very weak and sensitive to radiation damage. Here, in application to a poorly diffracting (d_min of 3.5 Å) and relatively large structure (1456 ordered residues), it is shown that data merged from multiple crystals can support SAD structure determination when no single data set is adequate.

Structures of human thymidylate synthase R163K with dUMP, FdUMP and gluta­thione show asymmetric ligand binding

A new crystal form of the R163K variant of human thymidylate synthase (hTS) with five subunits per asymmetric part of the unit cell, all with loop 181–197 in the active conformation, is reported.

New clues in the allosteric activation of DNA cleavage by SgrAI: structures of SgrAI bound to cleaved primary-site DNA and uncleaved secondary-site DNA

The structures of SgrAI bound to secondary-site DNA and Ca²⁺ or Mg²⁺, as well as bound to cleaved primary-site DNA and Mg²⁺, are presented and show similar overall conformations interpreted as the low-activity form of the enzyme. A third Mg²⁺ ion-binding site is found in the structure with cleaved primary-site DNA, as predicted by the two-metal-ion mechanism.

Notes for authors 2011