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Journal Issue - Volume 18 Issue 6 (June 2009)

Abstract Coactivator‐associated arginine methyltransferase 1 (CARM1), originally defined as a coactivator for steroid receptors, is a member of the protein arginine methyltransferases. Here, we report the discovery and characterization of an automethylation event by AgCARM1, a CARM1 homologue in the mosquito Anopheles gambiae, using top–down high resolution tandem mass spectrometry, which allows fine mapping of modifications in the intact...

Abstract The active site of ß‐galactosidase (E. coli) contains a Mg2+ ion ligated by Glu‐416, His‐418 and Glu‐461 plus three water molecules. A Na+ ion binds nearby. To better understand the role of the active site Mg2+ and its ligands, His‐418 was substituted with Asn, Glu and Phe. The Asn‐418 and Glu‐418 variants could be crystallized and the structures were shown to be very similar to native enzyme. The Glu‐418 variant showed increased mobility of some...

Abstract Computational protein design relies on a number of approximations to efficiently search the huge sequence space available to proteins. The fixed backbone and rotamer approximations in particular are important for formulating protein design as a discrete combinatorial optimization problem. However, the resulting coarse‐grained sampling of possible side‐chain terminal positions is problematic for the design of protein...

Abstract Although a quantitative relationship between sequence similarity and structural similarity has long been established, little is known about the impact of orthology on the relationship between protein sequence and structure. Among homologs, orthologs (derived by speciation) more frequently have similar functions than paralogs (derived by duplication). Here, we hypothesize that an orthologous pair will tend to exhibit greater...

Abstract Acidianus Filamentous Virus 1 (AFV1), isolated from acidic hot springs, is an enveloped lipid‐containing archaeal filamentous virus with a linear double‐stranded DNA genome. It infects Acidianus, which is a hyperthermostable archaea growing at 85°C and acidic pHs, below pH 3. AFV1‐99, a protein of 99 amino acids of unknown function, has homologues in the archaeal virus families Lipothrixviridae and Rudiviridae. We determined the...

Abstract Linear groups—polypeptide conformations based on a single repeating ϕ,ψ‐pair—are a foundational concept in protein structure, yet how they are presented in textbooks is based largely on theoretical studies from the early days of protein structure analysis. Now, ultra‐high resolution protein structures provide a resource for an accurate empirical and systematic assessment of the linear groups that truly exist in proteins....

Abstract In probing the mechanism of inhibition of hypoxia inducible factor (HIF‐1) by campothecins, we investigated the ability of human topoisomerase I to bind and cleave HIF‐1 response element (HRE), which contains the known camptothecin‐mediated topoisomerase I cleavage site 5′‐TG. We observed that the selection of 5′‐TG by human topoisomerase I and topotecan depends to a large extent on the specific flanking sequences, and that...

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