9 research outputs found
On the conservation of the slow conformational dynamics within the amino acid kinase family: NAGK the paradigm
N-Acetyl-L-Glutamate Kinase (NAGK) is the structural paradigm for examining the catalytic mechanisms and dynamics of amino acid kinase family members. Given that the slow conformational dynamics of the NAGK (at the microseconds time scale or slower) may be rate-limiting, it is of importance to assess the mechanisms of the most cooperative modes of motion intrinsically accessible to this enzyme. Here, we present the results from normal mode analysis using an elastic network model representation, which shows that the conformational mechanisms for substrate binding by NAGK strongly correlate with the intrinsic dynamics of the enzyme in the unbound form. We further analyzed the potential mechanisms of allosteric signalling within NAGK using a Markov model for network communication. Comparative analysis of the dynamics of family members strongly suggests that the low-frequency modes of motion and the associated intramolecular couplings that establish signal transduction are highly conserved among family members, in support of the paradigm sequence→structure→dynamics→function © 2010 Marcos et al
The Complete Genome Sequence of ‘Candidatus Liberibacter solanacearum’, the Bacterium Associated with Potato Zebra Chip Disease
Zebra Chip (ZC) is an emerging plant disease that causes aboveground decline of
potato shoots and generally results in unusable tubers. This disease has led to
multi-million dollar losses for growers in the central and western United States
over the past decade and impacts the livelihood of potato farmers in Mexico and
New Zealand. ZC is associated with ‘Candidatus
Liberibacter solanacearum’, a fastidious alpha-proteobacterium that is
transmitted by a phloem-feeding psyllid vector, Bactericera
cockerelli Sulc. Research on this disease has been hampered by a
lack of robust culture methods and paucity of genome sequence information for
‘Ca. L. solanacearum’. Here we present the
sequence of the 1.26 Mbp metagenome of ‘Ca. L.
solanacearum’, based on DNA isolated from potato psyllids. The coding
inventory of the ‘Ca. L. solanacearum’ genome was
analyzed and compared to related Rhizobiaceae to better
understand ‘Ca. L. solanacearum’ physiology and
identify potential targets to develop improved treatment strategies. This
analysis revealed a number of unique transporters and pathways, all potentially
contributing to ZC pathogenesis. Some of these factors may have been acquired
through horizontal gene transfer. Taxonomically, ‘Ca. L.
solanacearum’ is related to ‘Ca. L.
asiaticus’, a suspected causative agent of citrus huanglongbing, yet many
genome rearrangements and several gene gains/losses are evident when comparing
these two Liberibacter. species. Relative to ‘Ca. L.
asiaticus’, ‘Ca. L. solanacearum’ probably
has reduced capacity for nucleic acid modification, increased amino acid and
vitamin biosynthesis functionalities, and gained a high-affinity iron transport
system characteristic of several pathogenic microbes
Changes in Dynamics upon Oligomerization Regulate Substrate Binding and Allostery in Amino Acid Kinase Family Members
Oligomerization is a functional requirement for many proteins. The interfacial interactions and the overall packing geometry of the individual monomers are viewed as important determinants of the thermodynamic stability and allosteric regulation of oligomers. The present study focuses on the role of the interfacial interactions and overall contact topology in the dynamic features acquired in the oligomeric state. To this aim, the collective dynamics of enzymes belonging to the amino acid kinase family both in dimeric and hexameric forms are examined by means of an elastic network model, and the softest collective motions (i.e., lowest frequency or global modes of motions) favored by the overall architecture are analyzed. Notably, the lowest-frequency modes accessible to the individual subunits in the absence of multimerization are conserved to a large extent in the oligomer, suggesting that the oligomer takes advantage of the intrinsic dynamics of the individual monomers. At the same time, oligomerization stiffens the interfacial regions of the monomers and confers new cooperative modes that exploit the rigid-body translational and rotational degrees of freedom of the intact monomers. The present study sheds light on the mechanism of cooperative inhibition of hexameric N-acetyl-L-glutamate kinase by arginine and on the allosteric regulation of UMP kinases. It also highlights the significance of the particular quaternary design in selectively determining the oligomer dynamics congruent with required ligand-binding and allosteric activities