key: cord-0041528-u35ef238 authors: nan title: Graphical Abstract: ChemBioChem 1/2006 date: 2006-01-05 journal: Chembiochem DOI: 10.1002/cbic.200690002 sha: 0659203e03c55fdcf8e74fc89c6807b138b910b4 doc_id: 41528 cord_uid: u35ef238 nan Small but perfectly formed. A library of miniature protein variants was constructed that presented the minimal recognition epitope of the human doubleminute 2 oncoprotein (hDM2), which was derived from the activation domain of p53 (p53AD). This library was optimized (see scheme) to yield several miniature proteins with robust folds and nanomolar affinity for hDM2. The inhibitory activities of these miniature proteins correlated with the stability of the protein fold. This emphasizes the benefit of presenting the p53AD epitope on a miniature protein scaffold. R. Srinivasan, X. Huang, S. L. Ng, S. Q. Yao* Activity-Based Fingerprinting of Proteases Not inhibited. We have successfully synthesized and tested a panel of activity-based small-molecule probes that target different classes of proteases on the basis of their enzymatic activities and substrate specificities rather than their inhibition. We have demonstrated that these probes are useful for generating unique substrate fingerprint profiles of proteases in gel-based proteomic experiments. Preliminary results indicate that they might be equally amenable for microarray-based enzyme profiling experiments. M. Müller, J. He, C. Hertweck* Part of the queue. Biosynthesis of the cytostatic polyketide aureothin (1) in Streptomyces thioluteus was found to involve two tailoring steps (see scheme). Mutational biosynthesis of nor-deoxyaureothin (a-2) and a hydroxylated derivative (3), together with biotransformation experiments revealed a well-defined order for the polyketide-tailoring steps. Regioselective g-pyrone methylation was found to be the penultimate biosynthetic step prior to furan-ring formation. T. Müller, S. Moser, K.-H. Ongania, A. Pruzinska, S. Hçrtensteiner, B. Kräutler* A Divergent Path of Chlorophyll Breakdown in the Model Plant Arabidopsis thaliana A different kind of breakdown. The structure of At-NCC-3, a polar nonfluorescent chlorophyll catabolite (NCC) from the model plant Arabidopsis thaliana, deviates curiously from the known chlorophyll-breakdown pathway in higher plants: At-NCC-3 carries a hydroxymethyl group instead of a methyl group at C(7), a much discussed, specific structural link of the known NCCs with chlorophyll(ide) a. M. Venanzi,* E. Gatto, G. Bocchinfuso, A. Palleschi, L. Stella, F. Formaggio, C. Toniolo Dynamics of Formation of a Helix-Turn-Helix Structure in a Membrane-Active Peptide: A Time-Resolved Spectroscopic Study The characteristic time for the contact formation between two helical segments, a fundamental step in the protein-folding pathway, has been determined by time-resolved optical spectroscopies on a model bioactive peptide. J. López de la Osa, C. Gonzµlez,* R. Gargallo, M. Rueda, E. Cubero, M. Orozco,* A. AviÇó, R. Eritja* Getting rid of unwanted quadruplexes. Oligonucleotides carrying 8-amino-2'-deoxyguanosine form very stable triple-helical structures. In this paper, we show that 8-amino-2'-deoxyguanosines destabilize quadruplex DNA structures. This quadruplex-destabilization effect is very convenient for the design of triplex-forming oligonucleotides, making 8-aminopurines superior to other purine derivatives. O. Khersonsky, D. S. Tawfik* Chromogenic and Fluorogenic Assays for the Lactonase Activity of Serum Paraoxonases 5-Thioalkyl butyrolactones (1) are shown to be useful chromogenic/fluorogenic probes for determining lactonase activities, in particular of serum para-oxonase (PON1). These novel probes are suitable for measuring lactonase activity in complex biological samples, including sera, intact cells and cell lysates. Benzimidazole-based analogues of cisand trans-Epo A, 2 and 3, have been prepared through stereoselective total synthesis. Both compounds are highly potent antiproliferative agents, but the effects of side-chain replacement on cel-lular activity are ambivalent. While significantly enhanced potency is observed against a drug-sensitive human cancer cell line, 2 and 3 more susceptible to Pgp-mediated drug efflux than Epo A or trans-Epo A. P. Berthault,* G. Huber, P. T. Ha, L. Dubois, H. Desvaux, E. Guittet Study of the Hydrophobic Cavity of b-Cryptogein through Laser-Polarized Xenon NMR Spectroscopy Magnetization transfer. The cavity of b-cryptogein has been investigated by laser-polarized xenon NMR. Whereas 1 H and 13 C experiments do not show significant chemical shift variation with increasing xenon pressure, the use of polarization transfer from the dissolved noble gas to protons undoubtedly reveals an interaction site. Xenon biosensors can be used as sensitive, low-background, magnetic-resonance detectors for biomolecular events. Here we describe the necessary molecular parameters for obtaining optimal signal-to-noise and chemical shift sensitivity from a protein-bound xenon biosensor. The Dipeptide H-Trp-Glu-OH Shows Highly Antagonistic Activity Illuminating retaining endo-glycosidases. Mechanism-based probes were synthesized through conjugation of a biochemical tag, biotin (see picture), to a specific and efficient 2-deoxy-2-fluorosugar inactivator of retaining glycosidases. Experiments with pure glycosidases and the secreted proteome of Cellulomonas fimi illustrated the power of this approach for targeting and identification of retaining endo-xylanases in complex proteomes. A. Kupan, A. Saulire, S. Broussy, C. Seguy, G. Pratviel,* B. Meunier Guanine Oxidation by Electron Transfer: One-versus Two-Electron Oxidation Mechanism Radical leads to lesions: The fate of a guanine radical cation, the product of one-electron oxidation of guanine in DNA, was shown to follow a major pathway, deprotonation followed by trapping by O 2 (see scheme). This leads to imidazolone (Iz) as the major guanine lesion. A minor two-electron oxidation pathway was evidenced by the formation of guanine lesions like 8-oxo-7,8-dihydroguanine and tris(hydroxymethyl)aminomethane (Tris) adducts. Lack of lactone. The naturally occurring lipopolysaccharide (LPS) from Rhizobium sin-1 can antagonize the production of the tumor necrosis factor TNF-a by enteric LPS. As it is not known whether a 2-aminogluconolactone or 2-aminogluconate form is responsible for this property, compound 4, which contains a methyl ether at the C-5 hydroxy group preventing lactonization, was prepared and its proinflammatory properties were determined. Reverse Prenyltransferase in the Biosynthesis of Fumigaclavine C in Aspergillus fumigatus: Gene Expression, Purification, and Characterization of Fumigaclavine C Synthase FGAPT1 A putative prenyltransferase gene from Aspergillus fumigatus AF293-fgaPT1-was cloned and overexpressed in Escherichia coli. The His 6 -fusion FgaPT1 was purified to near homogeneity and characterized biochemically. This enzyme was found to convert fumigaclavine A (1) into fumigaclavine C (2) by attaching a dimethylallyl moiety to C-2 of the indole nucleus in a "reverse" manner. The biochemical properties of FgaPT1 have been investigated in this study. The Solution Structure of the AppA BLUF Domain: Insight into the Mechanism of Light-Induced Signaling NMR studies show that in the flavinbinding BLUF domain of AppA, a bluelight photoreceptor protein, considerable disorder is observed for residues near the flavin chromophore due to conformational exchange both in the dark and in the light-induced signaling state of AppA. Light-induced structural changes in a patch of surface residues provide a structural link between light absorption and signal-transduction events that inhibit the antirepressor function of AppA. I. Sielaff, A. Arnold, G. Godin, S. Tugulu, H.-A. Klok,* K. Johnsson* Protein Function Microarrays Based on Self-Immobilizing and Self-Labeling Fusion Proteins A simple and reliable approach for the generation of protein microarrays based on self-immobilizing fusion proteins is presented. Important features of the approach are the selectivity of the immobilization and the opportunity both to label and to immobilize the employed fusion proteins, which allows for the direct screening for protein-protein interactions. In addition, these protein microarrays can be used for the characterization of small molecule-protein interactions or post-translational modifications. BioSciences Citation Index, Chemistry Citation Index, ChemSciences Citation Index, Current Contents/Life Sciences Edition, Current Contents Connect When citing work presented in ChemBioChem-A Personal rates for members of a national chemical society, print only (including postage and handling charges E-mail: service@wiley-vch.de For readers in the rest of the world Members of the GDCh must place their orders directly at the publishers (via Subscription Service above). 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