Biomedical subjects

C L Lawson

Publications and source records attributed to C L Lawson.

23 records · Page 2Linked to original sources

PubMed1988

Flexibility of the DNA-binding domains of trp repressor.

An orthorhombic crystal form of trp repressor (aporepressor plus L-tryptophan ligand) was solved by molecular replacement, refined to 1.65 A resolution, and compared to the structure of the repressor in trigonal crystals. Even though these two crystal forms of repressor were grown under identical conditions, the refined structures have distinctly different conformations of the DNA-binding domains. Unlike the repressor/aporepressor structural transition, the conformational shift is not caused by the binding or loss of the L-tryptophan ligand. We conclude that while L-tryptophan binding is essential for forming a specific complex with trp operator DNA, the corepressor ligand does not lock the repressor into a single conformation that is complementary to the operator. This flexibility may be required by the various binding modes proposed for trp repressor in its search for and adherence to its three different operator sites.

Apoproteins↗

PubMedDate not supplied

Crystallization and preliminary X-ray analysis of Borrelia burgdorferi outer surface protein A (OspA) complexed with a murine monoclonal antibody Fab fragment.

The Borrelia burgdorferi outer surface lipoprotein OspA is a current focus for vaccine development to prevent Lyme disease infection. A soluble, recombinant form of the protein lacking the amino-terminal lipid membrane anchor was cocrystallized with the Fab fragment of an agglutinating mouse monoclonal antibody. The crystals belong to space group P2(1)2(1)2(1), with a = 90.0 A, b = 91.9 A, and c = 102.9 A and they were found to diffract to a maximum resolution of 2.8 A using synchrotron radiation.

Animals↗

PubMedDate not supplied

The three-dimensional structure of trp repressor.

The crystal structure of the Escherichia coli trp repressor has been solved to atomic resolution. The dimeric protein has a remarkable subunit interface in which five of each subunit's six helices are interlinked. The binding of L-tryptophan activates the aporepressor indirectly by fixing the orientation of the second helix of the helix-turn-helix motif and by moulding the details of the repressor's structure near the DNA binding surface.

Bacterial Proteins↗

PubMedDate not supplied

The crystal structure of trp aporepressor at 1.8 A shows how binding tryptophan enhances DNA affinity.

Comparison of the crystal structure of inactive unliganded trp aporepressor with that of trp repressor shows that binding tryptophan activates the dimer a thousandfold by moving two symmetrically-disposed flexible bihelical motifs. These flexible 'DNA-reading heads' flank a highly inflexible core domain formed by an unusual arrangement of interlocking alpha-helices from both subunits.

Apoproteins↗

PubMedDate not supplied

Clinical decision analysis modeling: short-term control of ventricular response rate in atrial fibrillation or atrial flutter-digoxin versus diltiazem.

OBJECTIVE: To develop a clinical decision model to compare the outcome of therapy with digoxin versus diltiazem for short-term control of ventricular response rate (VRR) in patients with atrial fibrillation or atrial flutter. DESIGN: Review of data from two studies that examined the percentages of response and frequency of adverse reactions in patients treated with intravenous digoxin or diltiazem to control VRR in atrial fibrillation or flutter. We constructed a clinical decision model and performed sensitivity analysis to determine if the model's predictions could be altered. SETTING: Large teaching, university hospitals. PARTICIPANTS: Adults age 18 years or older treated with intravenous digoxin or intravenous diltiazem for atrial fibrillation or flutter (VRR > or = 120 beats/min). Patients with severe heart failure New York Heart Association class III or IV, a surgical procedure prior to the exacerbation, or an acute myocardial infarction were excluded. MEASUREMENTS AND MAIN RESULTS: We measured VRR control after 1 and 24 hours of therapy (VRR < 100 beats/min or decrease of > or = 20%) and assessed the likelihood that a patient would suffer an adverse drug reaction. Initial assumptions were that the probability digoxin would achieve VRR control was 0.10 (95% confidence interval 0.04-0.20) at 1 hour and 0.70 (95% CI 0.56-0.80) at 24 hours; the probability that diltiazem would achieve VRR control was 0.94 (95% CI 0.82-0.99) at 1 hour and 0.83 (95% CI 0.68-0.94) at 24 hours; and the probability of no serious adverse drug reaction would be 0.90 (95% CI 0.80-0.96) for digoxin and 0.96 (95% CI 0.86-0.98) for diltiazem. RESULTS: Diltiazem was superior to digoxin with respect to the composite end point score at 1 hour (91.20 vs 17.29) and 24 hours (81.65 vs 66.43). Digoxin was superior to diltiazem at 24 hours only if the VRR was assumed to be at the highest 95% CI limit for digoxin and simultaneously at the lowest 95% CI for diltiazem (74.62 vs 68.63). CONCLUSIONS: Clinical decision analysis suggests that intravenous diltiazem is superior to intravenous digoxin in controlling VRR in patients with atrial fibrillation or flutter.

Adolescent↗