Mammalian genomes encode genes for more than 30 phospholipase A(2)s (PLA(2)s) or related enzymes, which are subdivided into several subgroups based on their structures, catalytic mechanisms, localizations and evolutionary relationships. More than one third of the PLA(2) enzymes belong to the secreted PLA(2) (sPLA(2)) family, which consists of low-molecular-weight, Ca(2+)-requiring extracellular...

Photocatalytic chemical synthesis by coupling abiotic photosensitizers to purified enzymes provides an effective way to overcome the low conversion efficiencies of natural photosynthesis while exploiting the high catalytic rates and selectivity of enzymes as renewable, earth-abundant electrocatalysts. However, the selective synthesis of multiple products requires more versatile approaches and s...

tRNA modifications are crucial for efficient and accurate protein translation, with defects often linked to disease. There are 7 cytoplasmic tRNA modifications in the yeast Saccharomyces cerevisiae that are formed by an enzyme consisting of a catalytic subunit and an auxiliary protein, 5 of which require only a single subunit in bacteria, and 2 of which are not found in bacteria. These enzymes ...

Human purine de novo synthesis pathway contains several multi-functional enzymes, one of which, tri-functional GART, contains three enzymatic activities in a single polypeptide chain. We have solved structures of two domains bearing separate catalytic functions: glycinamide ribonucleotide synthetase and aminoimidazole ribonucleotide synthetase. Structures are compared with those of homologous e...

Removal of ubiquitin from modified proteins is an important process to regulate the ubiquitin system. Roughly 100 dedicated enzymes for this purpose, the deubiquitinases, exist in human cells and are intricately involved in a wide variety of cellular processes, although many enzymes remain unstudied to date. The deubiquitinases consist of five enzyme families that contain USP, OTU, UCH, Josephi...

The 5' cap of human messenger RNA contains 2'-O-methylation of the first and often second transcribed nucleotide that is important for its processing, translation and stability. Human enzymes that methylate these nucleotides, termed CMTr1 and CMTr2, respectively, have recently been identified. However, the structures of these enzymes and their mechanisms of action remain unknown. In the present...

Type I restriction endonucleases are intriguing, multifunctional complexes that restrict DNA randomly, at sites distant from the target sequence. Restriction at distant sites is facilitated by ATP hydrolysis-dependent, translocation of double-stranded DNA towards the stationary enzyme bound at the recognition sequence. Following restriction, the enzymes are thought to remain associated with the...

In 1998 John Pople and Walter Kohn shared the Nobel Prize in Chemistry for the development of wave-function theory (WFT) and density-functional theory (DFT) methods, respectively. In 2013 the Chemistry Nobel Prize was awarded to Martin Karplus, Michael Levitt, and Arieh Warshel for the development of multi-scale methods. These electronic structure methods cover a wide range of accuracy and appl...

Evidence from published nuclear magnetic resonance studies of enzyme-substrate and enzyme-inhibitor systems systems shows that substrates are confined at the active site of the enzyme, have a relatively long residence time, and tumble in solution as an enzyme-substrate complex. The consequences of this "substrate anchoring" with regard to the catalytic power of enzymes are considered. It appear...

The principal methyl donor of the cell, S-adenosylmethionine (SAMe), is produced by the highly conserved family of methionine adenosyltranferases (MATs) via an ATP-driven process. These enzymes play an important role in the preservation of life, and their dysregulation has been tightly linked to liver and colon cancers. We present crystal structures of human MATα2 containing various bound ligan...