Notable

M. Gray, S.M. Honigberg, "Effect of chromosomal locus, GC content and length of homology on PCR-mediated targeted gene replacement in Saccharomyces," Nucleic Acids Research, 29:5156-62, Dec. 15, 2001. F1000 Rating: Recommended "While gene knockouts or replacements are easily and commonly done in yeast, the targeting efficiency is quite variable. The authors have systematically evaluated key parameters and found that a GC content of at least 40% in the regions of homology improves targeting efficiency. Surprisingly, changing the length of targeting homology from 40 to 60 bp had little effect." —Janet Lindsley, University of Utah, US Genomes & Genomics R. Tompa et al., "Genome-wide profiling of DNA methylation reveals transposon targets of CHROMOMETHYLASE3," Current Biology,12:65-8, Jan. 8, 2002. F1000 Rating: Recommended "A new technique can be used to monitor cytosine methylation across many genomic sites using microarrays. Using this technique, the authors investigate the targets of two different Arabidopsis methyltransferases, CMT3 and MET1. One of the take-home messages is that CMT3 preferentially targets transposon sequences in the Arabidopsis genome. The authors stress that this is a flexible and broadly applicable technique that can be used for cytosine methylation profiling in many systems, including human tumors." —Eric Richards, Washington University, St. Louis, US Bioinformatics J. Gough, C. Chothia, "SUPERFAMILY: HMMs representing all proteins of known structure. SCOP sequence searches, alignments and genome assignments," Nucleic Acids Research, 30:268-72, Jan. 1, 2002. F1000 Rating: Must Read "Gough and Chothia describe a particular protocol for using hidden Markov models (HMMs) for threading; that is, for finding proteins of similar folds but very diverged sequence. While this approach is not new, the particular protocol appears to profit ideally from the strengths of HMMs." —Burkhard Rost, Columbia University, New York, US X. de La Cruz et al., "Use of structure comparison methods for the refinement of protein structure predictions. I. Identifying the structural family of a protein from low-resolution models," Proteins, 46:72-84, Jan. 1, 2002. F1000 Rating: Recommended "This approach combines low-resolution predictions of protein structure from threading with comparative modeling and structural alignment to predict 3D structure. The particular novelty of the method lies in the way existing methods are combined. The more protein structures that are experimentally known, the more we may hope to identify short fragments in the known structures that only have to be assembled correctly to predict structure; the method described here addresses that goal." —Burkhard Rost Virology G. Kochs et al., "Self-assembly of human MxA GTPase into highly-ordered dynamin-like oligomers," Journal of Biological Chemistry, Published online, Feb. 14, 2002 [10.1074/jbc.M200244200] F1000 Rating: Recommended "The mode of antiviral action of the interferon-inducible dynamin-like GTPases, the Mx proteins, is still not known. Here it is shown that GTP binding in vitro causes human MxA to self-assemble into helical filaments, a process resembling the GTP-dependent polymerization of dynamin. The authors see these results as supporting the idea that Mx polymerization may play a role in the capture of viral nucleocapsids in vitro. Previous results from this group showing direct interaction between Mx and viral nucleocapsid proteins are consistent with this hypothesis." —Jonathan Howard, Institut fur Genetik, Germany Combinatorial Chemistry J. Goldberg et al., "Erythropoietin mimetics derived from solution phase combinatorial libraries," Journal of the American Chemical Society, 124:544-55, Jan. 30, 2002. F1000 Rating: Recommended Recombinant erythropoietin (EPO), a 34-kDa glycoprotein hormone, has been used successfully in clinical applications. However, an effective small molecule mimetic could advantageously replace the recombinant protein. Focusing on the erythropoietin receptor (EPOr) family, these researchers demonstrate the power of combinatorial chemistry to identify promising lead compounds, which act as agonist ligands for protein homodimerization. "A deconvolutive screening, using a protein binding assay of a soluble library of 600 dimeric iminodiacetic acid diamides, as mixtures of 10 compounds, provided a number of good binders of EPOr. Further optimization with oligomeric analogues led for the first time to a class of relatively small molecules functioning as mimetics of EPO." —Dennis Hall, University of Alberta, Canada Protein Engineering J.M. Zhou et al., "A novel strategy by the action of ricin that connects phenotype and genotype without loss of the diversity of libraries," Journal of the American Chemical Society, 124:538-43, Jan. 30, 2002. F1000 Rating: Recommended "This work presents a novel way of solving the key problem of high throughput screening for protein engineering: how to keep the phenotype and genotype physically associated. The authors use ricin to form a stable complex between the ribosome, an mRNA molecule, and the translated protein. They demonstrate the ability to screen in a couple of fairly simple systems, and claim this can be used as a simple and reliable screening process." —Mark Nelson, E.I. DuPont de Nemours & Co., US Q. Liu et al., "Validated zinc finger protein designs for all 16 GNN DNA triplet targets," Journal of Biological Chemistry, 277:3850-6, Feb. 8, 2002. F1000 Rating: Recommended "The authors report the basis for design of sequence-specific DNA binding proteins for potential use in gene regulation and nanobiotechnology. A combination of screening and rational design was used to discover zinc-finger peptide sequences relatively specific for each of the possible triplet codons. Assembly of multiple modules gives a process for developing proteins to bind to one's favorite sequence of DNA, whether as a repressor, a promoter, or to construct a DNA-based device." —Mark Nelson

Notable

Genomes & Genomics

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