The Catalytic Mechanisms of Binuclear Metallohydrolases

Abstract

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

The TP0796 Lipoprotein of Treponema pallidum Is a Bimetal-dependent FAD Pyrophosphatase with a Potential Role in Flavin Homeostasis

“…This assessment was confirmed via the refined electron density. The bimetal distance of 3.3 Å corresponds to the range of 3-4 Å commonly observed for binuclear metallohydrolases (43), and the monodentate aspartate bridging the metal centers has, for example, been observed in the human and E. coli ecto-5Ј-nucleotidase structures (44,45).…”

The UDP-diacylglucosamine Pyrophosphohydrolase LpxH in Lipid A Biosynthesis Utilizes Mn2+ Cluster for Catalysis

“…These enzymes perform catalysis using an ordered shell of water molecules and divalent or trivalent metal cofactors coordinated by conserved residues of the metallophosphoesterase motif (11,12). It has been postulated that the metal ions serve to bridge an oxide that performs a nucleophilic attack, to stabilize the formation of a phosphorane intermedi-ate, and to coordinate a nucleophilic hydroxyl group to allow for deprotonation (12,13).…”

“…It has been postulated that the metal ions serve to bridge an oxide that performs a nucleophilic attack, to stabilize the formation of a phosphorane intermedi-ate, and to coordinate a nucleophilic hydroxyl group to allow for deprotonation (12,13). Besides calcineurin, enzymes of the CLP superfamily also include protein serine/threonine phosphatases (14), purple acid phosphatases (15), nucleotidases, sphingomyelin phosphodiesterases (16), exonucleases, and cyclic nucleotide phosphodiesterases (11). These enzymes have broad functions but are thought to have evolved from the same ancestor (17).…”

Identification of Purple Acid Phosphatase Inhibitors by Fragment‐Based Screening: Promising New Leads for Osteoporosis Therapeutics

“…Key words: X-ray, crystallography, drug design, fragment screening, purple acid phosphatase, osteoporosis Purple acid phosphatases (PAP) are metalloenzymes that hydrolyse phosphate esters and anhydrides, generally at low pH values (1). The distinctive purple colour of these enzymes is due to a metal to ligand charge transfer from a tyrosine phenolate to a chromophoric Fe(III) (2,3).…”

“…Mammalian PAP is a 35 kDa monomeric protein also known as tartrate-resistant acid phosphatase (TRAP or TRAcP). In contrast, plant PAP is a 110 kDa homodimer, with each subunit consisting of two domains, an N-terminal one whose function is unknown and a catalytic C-terminal domain that strongly resembles the overall structure of the mammalian enzyme (1). Crystal structures of human (8), pig (9), rat (10,11) and plant PAPs (12,13) have been determined and show that the amino acid ligands of the metal ions are completely conserved across plant and animal PAPs, but there are some differences in the identities of the residues that line the active site.…”