Cell cycle time in the root apical meristem of angiosperms and its dependence on holoploid DNA content.

In the angiosperm root apical meristem, the holoploid DNA content is not directly related to cell cycle time. Instead, ploidy, chromosome number, and taxa emerge as key factors that influence this interaction. It is commonly considered that cell cycle time in the angiosperm root apical meristem is directly related to the holoploid DNA content, and this is one of the manifestations of the nucleotypic effect.

Global analysis of an exponential model of cell proliferation for estimation of cell cycle duration in the root apical meristem of angiosperms.

Background And Aims: Information on cell cycle duration (T) in the root apical meristem (RAM) provides insight into root growth, development and evolution. We have previously proposed a simple method for evaluating T based on the dynamics of root growth (V), the number of cells in the RAM (Nm) and the length of fully elongated cells (l), which we named the rate-of-cell-production (RCP) method. Here, a global analysis was performed to confirm the reliability of this method in a range of angiosperm species and to assess the advantages of this approach.

Poxvirus uracil-DNA glycosylase-An unusual member of the family I uracil-DNA glycosylases.

Uracil-DNA glycosylases are ubiquitous enzymes, which play a key role repairing damages in DNA and in maintaining genomic integrity by catalyzing the first step in the base excision repair pathway. Within the superfamily of uracil-DNA glycosylases family I enzymes or UNGs are specific for recognizing and removing uracil from DNA. These enzymes feature conserved structural folds, active site residues and use common motifs for DNA binding, uracil recognition and catalysis.

The processivity factor complex of feline herpes virus-1 is a new drug target.

Feline herpes virus-1 (FHV-1) is ubiquitous in the cat population and is a major cause of blindness for which antiviral drugs, including acyclovir, are not completely effective. Recurrent infections, due to reactivation of latent FHV-1 residing in the trigeminal ganglia, can lead to epithelial keratitis and stromal keratitis and eventually loss of sight. This has prompted the medical need for an antiviral drug that will specifically inhibit FHV-1 infection.

A novel target and approach for identifying antivirals against molluscum contagiosum virus.

The dermatological disease molluscum contagiosum (MC) presents as lesions restricted solely to the skin. The poxvirus molluscum contagiosum virus (MCV) is responsible for this skin disease that is easily transmitted through casual contact among all populations, with greater frequency in children and immunosuppressed individuals. In addition, sexual transmission of MCV in adolescents and adults is a health concern.

Design of potent poxvirus inhibitors of the heterodimeric processivity factor required for viral replication.

Smallpox constitutes a major bioterrorism threat, which underscores the need to develop antiviral drugs for rapid response in the event of an attack. Viral processivity factors are attractive drug targets in being both specific and essential for their cognate DNA polymerases to synthesize extended strands of DNA. An in silico model of the vacinnia virus processivity factor, comprised of the A20 and D4 heterocomplex, was constructed and used for lead optimization of an indole-based scaffold identified earlier from a high-throughput screening.

Anthrax edema factor potency depends on mode of cell entry.

Anthrax edema factor (EF) is a highly active calmodulin-dependent adenylyl cyclase toxin that can potently raise intracellular cAMP levels causing a broad range of tissue damage. EF needs anthrax protective antigen (PA) to enter into the host cell and together they form edema toxin. Here, we examine factors that are critical for edema toxin cell entry and potency.

Calcium-independent calmodulin binding and two-metal-ion catalytic mechanism of anthrax edema factor.

Edema factor (EF), a key anthrax exotoxin, has an anthrax protective antigen-binding domain (PABD) and a calmodulin (CaM)-activated adenylyl cyclase domain. Here, we report the crystal structures of CaM-bound EF, revealing the architecture of EF PABD. CaM has N- and C-terminal domains and each domain can bind two calcium ions.

Structural and kinetic analyses of the interaction of anthrax adenylyl cyclase toxin with reaction products cAMP and pyrophosphate.

Anthrax edema factor (EF) raises host intracellular cAMP to pathological levels through a calcium-calmodulin (CaM)-dependent adenylyl cyclase activity. Here we report the structure of EF.CaM in complex with its reaction products, cAMP and PP(i).

Structure of anthrax edema factor-calmodulin-adenosine 5'-(alpha,beta-methylene)-triphosphate complex reveals an alternative mode of ATP binding to the catalytic site.

Anthrax edema factor (EF) is a key virulence factor secreted by Bacillus anthracis. Here, we report a structure, at 3.0 A resolution, of the catalytic domain of EF (EF3) in complex with calmodulin (CaM) and adenosine 5'-(alpha,beta-methylene)-triphosphate (AMPCPP).

Selective inhibition of anthrax edema factor by adefovir, a drug for chronic hepatitis B virus infection.

Edema factor (EF), a key virulence factor in anthrax pathogenesis, has calmodulin (CaM)-activated adenylyl cyclase activity. We have found that adefovir dipivoxil, a drug approved to treat chronic infection of hepatitis B virus, effectively inhibits EF-induced cAMP accumulation and changes in cytokine production in mouse primary macrophages. Adefovir diphosphate (PMEApp), the active cellular metabolite of adefovir dipivoxil, inhibits the adenylyl cyclase activity of EF in vitro with high affinity (K(i) = 27 nM).