Pseudomonas aeruginosa 4-Amino-4-Deoxychorismate Lyase: Spatial Conservation of an Active Site Tyrosine and Classification of Two Types of Enzyme

4-Amino-4-deoxychorismate lyase (PabC) catalyzes the formation of 4-aminobenzoate, and release of pyruvate, during folate biosynthesis. This is an essential activity for the growth of Gram-negative bacteria, including important pathogens such as Pseudomonas aeruginosa. A high-resolution (1.75 Å) crystal structure of PabC from P. aeruginosa has been determined, and sequence-structure comparisons with orthologous structures are reported. Residues around the pyridoxal 5′-phosphate cofactor are highly conserved adding support to aspects of a mechanism generic for enzymes carrying that cofactor. However, we suggest that PabC can be classified into two groups depending upon whether an active site and structurally conserved tyrosine is provided from the polypeptide that mainly forms an active site or from the partner subunit in the dimeric assembly. We considered that the conserved tyrosine might indicate a direct role in catalysis: that of providing a proton to reduce the olefin moiety of substrate as pyruvate is released. A threonine had previously been suggested to fulfill such a role prior to our observation of the structurally conserved tyrosine. We have been unable to elucidate an experimentally determined structure of PabC in complex with ligands to inform on mechanism and substrate specificity. Therefore we constructed a computational model of the catalytic intermediate docked into the enzyme active site. The model suggests that the conserved tyrosine helps to create a hydrophobic wall on one side of the active site that provides important interactions to bind the catalytic intermediate. However, this residue does not appear to participate in interactions with the C atom that undergoes an sp2 to sp3 conversion as pyruvate is produced. The model and our comparisons rather support the hypothesis that an active site threonine hydroxyl contributes a proton used in the reduction of the substrate methylene to pyruvate methyl in the final stage of the mechanism

Quantifying the convergence speed of LMS adaptive FIR filter with autoregressive inputs

In general the least mean squares adaptive finite impulse response (FIR) filter converges more slowly with an increase in filter length and input signal correlation level. An explicit expression is presented relating the convergence speed of this adaptive filter to the FIR filter length and the correlation characteristics of autoregressive (AR) modelled input signals. The expression provides a simple means for justifying (or not) the cost of input signal whitening techniques within for example acoustic echo cancellation, in which very large FIR filter lengths and highly correlated AR modelled speech input signals occur

BREAKTHROUGH PAIN DURING LABOR: CONVENTIONAL PATIENT CONTROLLED EPIDURAL ANALGESIA WITHOUT BACKGROUND INFUSION VS PROGRAMMED INTERMITTENT EPIDURAL BOLUSES: A RANDOMIZED DOUBLE BLIND STUDY IN NULLIPAROUS WOMEN

status: publishe

Classes of oppositional-defiant behavior: Concurrent and predictive validity

Background: Oppositional defiant disorder (ODD) has components of both irritability and defiance. It remains unclear whether children with variation in these domains have different adult outcomes. This study examined the concurrent and predictive validity of classes of oppositional defiant behavior. Methods: Latent class analysis was performed on the oppositional defiant problems scale of the Child Behavior Checklist in two samples, one in the US (the Achenbach Normative Sample, N = 2029) and one in the Netherlands (the Zuid-Holland Study, N = 2076). A third sample of American children (The Vermont Family Study, N = 399) was examined to determine concurrent validity with DSM diagnoses. Predictive validity over 14 years was assessed using the Zuid-Holland Study. Results: Four classes of oppositional defiant problems were consistent in the two latent class analyses: No Symptoms, All Symptoms, Irritable, and Defiant. Individuals in the No Symptoms Class were rarely diagnosed concurrently with ODD or any future disorder. Individuals in the All Symptoms Class had an increased frequency of concurrent childhood diagnosis of ODD and of violence in adulthood. Subjects in the Irritable Class had low concurrent diagnosis of ODD, but increased odds of adult mood disorders. Individuals in the Defiant Class had low concurrent diagnosis of ODD, but had increased odds of violence as adults. Conclusions: Only children in the All Symptoms class were likely to have a concurrent diagnosis of ODD. Although not diagnosed with ODD, children in the Irritable Class were more likely to have adult mood disorders and children in the Defiant Class were more likely to engage in violent behavior