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Current Issue

Volume 17 Issue 8: August 27, 2010

Next issue: September 24, 2010

Included in this issue

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Featured Article

The Featured Articles are freely available to all readers.

The glycerophospho-metabolome and its influence on amino acid homeostasis revealed by brain metabolomics of GDE1(-/-) mice

Florian Kopp, Toru Komatsu, Daniel K. Nomura, Sunia A. Trauger, Jason R. Thomas, Gary Siuzdak, Gabriel M. Simon, and Benjamin F. Cravatt

 

The function of glycerophosphodiesterase (GDE) enzymes in mammalian organisms is largely unknown. Here Kopp et al. use mouse genetics and untargeted metabolomics to show that GDE1 regulates a set of glycerophospho (GroP) metabolites in brain, including both known (GroP-inositol) and novel (GroP-serine and GroP-glycerate) natural products. The metabolomic profiles also revealed that serine was significantly reduced in brains of GDE1-disrupted mice, thus designating GroPSer as a reservoir for free serine in the nervous system. Taken together, these findings indicate that the mammalian "GroP-metabolome" is quite diverse in structure and function and designate GDE1 as one of its principal enzymatic regulators in vivo.

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In this Issue

		Fighting Malaria with Improved Arsenal Malaria remains one of the most devastating infectious diseases causing close to a million deaths per year. In this work Deu et al. describe the use of small molecule inhibitors and activity-based probes to demonstrate that inhibition of dipeptidyl aminopeptidase 1 impairs parasite growth both in vitro and in a mouse model of malaria, validating this cysteine protease as an anti-malarial target.
		Intermediate in Cytochrome P450 Epoxidation PimD is a cytochrome P450 monooxygenase with native epoxidase activity that is critical in the biosynthesis of the polyene macrolide antibiotic pimaricin. Kells et al. present an X-ray structure of PimD, both substrate-free and in complex with 4,5-deepoxypimaricin presenting evidence that epoxidation of 4,5-deepoxipimaricin proceeds via a hydroperoxoferric intermediate .
		From an Esterase to a Hydroxynitrile Lyase Proteins with similar structure can catalyze different chemical reactions. To learn how enzymes catalyze reactions, how they evolve to catalyze new reactions, and to create new enzymes for synthesis, researchers engineer new types of catalytic activity into enzymes. Padhi et al. now show that two amino acid substitution converts an esterase into a hydroxynitrile lyases.
		Pantothenate Kinase 3 Regulation by Small Molecules Pantothenate kinase (PanK) catalyzes the rate-controlling step in coenzyme A (CoA) biosynthesis. Biochemical analysis, reported by Leonardi et al., indicates that pantothenate binds in a tunnel adjacent to the active site. An HTS for PanK3 inhibitors and activators identified thiazolidinediones, sulfonylureas and steroids as inhibitors, and fatty acyl-amides and tamoxifen as activators.

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2, 5, 10 Years Ago

A look back at some of the stories that enticed chemical biology community in August issues of Chemistry & Biology from 2, 5 and 10 years ago.

C&B, August 2008: 2 Years Ago
GFP Family: Structural Insights into Spectral Tuning
Alexey A. Pakhomov and Vladimir I. Martynov
Chem. Biol. 15(8), 755-764

Covalent Inhibitors of Human Monoacylglycerol Lipase: Ligand-Assisted Characterization of the Catalytic Site by Mass Spectrometry and Mutational Analysis
Nikolai Zvonok, Lakshmipathi Pandarinathan, John Williams, Meghan Johnston, Ioannis Karageorgos, David R. Janero, Srinivasan C. Krishnan and Alexandros Makriyannis
Chem. Biol. 15(8), 854-862

C&B, August 2005: 5 Years Ago
A Ribozyme for the Aldol Reaction
Stefan Fusz, Alexander Eisenführ, Seergazhi G. Srivatsan, Alexander Heckel and Michael Famulok
Chem. Biol. 12(8), 941-950

Calcium Ions Effectively Enhance the Effect of Antisense Peptide Nucleic Acids Conjugated to Cationic Tat and Oligoarginine Peptides
Takehiko Shiraishi, Stanislava Pankratova and Peter E. Nielsen
Chem. Biol. 12(8), 923-929

C&B, August 2000: 10 Years Ago
Epoxide electrophiles as activity-dependent cysteine protease profiling and discovery tools
Doron Greenbaum, Katalin F Medzihradszky, Alma Burlingame, and Matthew Bogyo
Chem. Biol. 7(8), 569-581

The biosynthetic gene cluster for the antitumor drug bleomycin from Streptomyces verticillus ATCC15003 supporting functional interactions between nonribosomal peptide synthetases and a polyketide synthase
Liangcheng Du, César Sánchez, Mei Chen, Daniel J Edwards and Ben Shen
Chem. Biol. 7(8), 623-642