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Biomedical subjects

R Aurora

Publications and source records attributed to R Aurora.

13 recordsLinked to original sources
PubMed2002

Manganese transport and its regulation in bacteria.

Regulation of manganese acquisition by bacteria occurs by both biochemical regulation of the activity of the transporters and transcriptional regulation of gene expression. Structural analysis suggests that calcium ions may regulate the function of an Mn ATP-binding cassette (ABC)-permease in Synechocystis 6803, a cyanobacterium, as well as in a number of other bacteria. The expression of genes encoding the manganese transporter in Synechocystis 6803 is regulated by a two-component signal-transduction mechanism that has not been previously observed for manganese and zinc transport in bacteria.

Amino Acid Sequence↗
PubMed2000

Impact of multicentricity on clinical outcome in patients with T1-2, N0-1, M0 breast cancer.

BACKGROUND: The objective was to determine the impact of multicentric breast cancer on recurrence and survival and to evaluate the current tumor, node, metastasis staging system recommendations for multicentricity in the breast. METHODS: This study included 284 nonpregnant patients with T1-2, N0-1, M0 breast cancer, without previous cancer, who were treated by modified radical mastectomy followed by doxorubicin-based adjuvant chemotherapy. Clinical and pathological data were collected retrospectively and survival was calculated from the date of initial diagnosis using the Kaplan-Meier method. RESULTS: The median follow-up time was 8 years (range, 0.3-24.0), and the median age was 47 years (range, 23-76). The median clinical size of the index tumor was 2.5 cm. In 17% of patients, the clinical nodal status was N1. In 84% of patients, pathology of the index lesion was invasive ductal +/- in situ. Multicentric breast cancer was detected in 60 patients (21%): 30 patients with two lesions, 13 patients with three lesions, and 17 patients with four or more lesions. Locoregional recurrence, contralateral breast cancer, distant metastasis, and survival (disease-specific and disease-free) were similar in both groups of multicentric versus unicentric breast tumors. There was a significant difference between groups in estrogen receptor and axillary lymph node positivity, but these did not contribute significantly to outcome on multivariate analysis. CONCLUSIONS: Multicentricity does not increase the risk of poor outcomes in patients with early-stage breast cancer. This supports the current recommendations of the tumor, node, metastasis staging system that tumor size should be based on the diameter of the largest lesion in patients with multicentric breast cancer.

Adult↗
PubMed2000

Respiratory emergencies.

Respiratory emergencies may originate from disease in the airways, thoracic vessels, and pulmonary parenchyma. Airway obstruction may be amenable to bronchoscopic therapies, including laser ablation photodynamic therapy (PDT) and stent placement. Asthma is common, but may be mimicked by endobronchial metastasis. Superior vena cava syndrome (SVCS) is seen most commonly with bronchogenic carcinoma and lymphoma. Emergent treatment need not precede tissue diagnosis in the absence of associated tracheal obstruction. Pulmonary embolism (PE) may now be diagnosed with spiral computed tomography (CT), but ventilation perfusion scintigraphy remains the first-line test. Parenchymal lung disease may result from infections, with neoplastic and iatrogenic etiologies. The incidence of Pneumocystis carinii pneumonia (PCP) is increasing among cancer patients, but it can be prevented by prophylaxis. Attempts to treat adult respiratory distress syndrome (ARDS) through modification of inflammatory mediators have been disappointing, and the prognosis remains poor.

Adult↗
PubMed1999

A protein taxonomy based on secondary structure.

Does a protein's secondary structure determine its three-dimensional fold? This question is tested directly by analyzing proteins of known structure and constructing a taxonomy based solely on secondary structure. The taxonomy is generated automatically, and it takes the form of a tree in which proteins with similar secondary structure occupy neighboring leaves. Our tree is largely in agreement with results from the structural classification of proteins (SCOP), a multidimensional classification based on homologous sequences, full three-dimensional structure, information about chemistry and evolution, and human judgment. Our findings suggest a simple mechanism of protein evolution.

Algorithms↗
PubMed1999

Identifying two ancient enzymes in Archaea using predicted secondary structure alignment.

It is now possible to compare life forms at high levels of detail and completeness due to the increasing availability of whole genomes from all three domains. However, exploration of interesting hypotheses requires the ability to recognize a correspondence between proteins that may since have diverged beyond the threshold of detection by sequence-based methods. Since protein structure is far better conserved than protein sequence, structural information can enhance detection sensitivity, and this is the basis for the field of structural genomics. Demonstrating the effectiveness of this approach, we identify two important but previously elusive Archaeal enzymes: a homolog of dihydropteroate synthase and a thymidylate synthase. The former is especially noteworthy in that no Archaeal homolog of a bacterial folate biosynthetic enzyme has been found to date. Experimental confirmation of the deduced activity of both enzymes is described. Identification of two different proteins was attempted deliberately to help allay concern that predictive success is merely a lucky accident.

Archaea↗
PubMed1998

Seeking an ancient enzyme in Methanococcus jannaschii using ORF, a program based on predicted secondary structure comparisons.

We have developed a simple procedure to identify protein homologs in genomic databases. The program, called ORF, is based on comparisons of predicted secondary structure. Protein structure is far better conserved than amino acid sequence, and structure-based methods have been effective in exploiting this fact to find homologs, even among proteins with scant sequence identity. ORF is a secondary structure-based method that operates solely on predictions from sequence and requires no experimentally determined information about the structure. The approach is illustrated by an example: Thymidylate synthase, a highly conserved enzyme essential to thymidine biosynthesis in both prokaryotes and eukaryotes, is thought to be used by Archaea, but a corresponding gene has yet to be identified. Here, a candidate thymidylate synthase is identified as a previously unassigned open reading frame from the genome of Methanococcus jannaschii, viz., MJ0757. Using primary structure information alone, the optimally aligned sequence identity between MJ0757 and Escherichia coli thymidylate synthase is 7%, well below the threshold of sensitivity for detection by sequence-based methods.

Amino Acid Sequence↗
PubMed1998

Helix capping.

Helix-capping motifs are specific patterns of hydrogen bonding and hydrophobic interactions found at or near the ends of helices in both proteins and peptides. In an alpha-helix, the first four >N-H groups and last four >C=O groups necessarily lack intrahelical hydrogen bonds. Instead, such groups are often capped by alternative hydrogen bond partners. This review enlarges our earlier hypothesis (Presta LG, Rose GD. 1988. Helix signals in proteins. Science 240:1632-1641) to include hydrophobic capping. A hydrophobic interaction that straddles the helix terminus is always associated with hydrogen-bonded capping. From a global survey among proteins of known structure, seven distinct capping motifs are identified-three at the helix N-terminus and four at the C-terminus. The consensus sequence patterns of these seven motifs, together with results from simple molecular modeling, are used to formulate useful rules of thumb for helix termination. Finally, we examine the role of helix capping as a bridge linking the conformation of secondary structure to supersecondary structure.

Hydrogen Bonding↗
PubMed1994

Rules for alpha-helix termination by glycine.

A predictive rule for protein folding is presented that involves two recurrent glycine-based motifs that cap the carboxyl termini of alpha helices. In proteins, helices that terminated in glycine residues were found predominantly in one of these two motifs. These glycine structures had a characteristic pattern of polar and apolar residues. Visual inspection of known helical sequences was sufficient to distinguish the two motifs from each other and from internal glycines that fail to terminate helices. These glycine motifs--in which the local sequence selects between available structures--represent an example of a stereochemical rule for protein folding.

Amino Acid Sequence↗
PubMed1994

Crystal structure of the Oct-1 POU domain bound to an octamer site: DNA recognition with tethered DNA-binding modules.

The structure of an Oct-1 POU domain-octamer DNA complex has been solved at 3.0 A resolution. The POU-specific domain contacts the 5' half of this site (ATGCAAAT), and as predicted from nuclear magnetic resonance studies, the structure, docking, and contacts are remarkably similar to those of the lambda and 434 repressors. The POU homeodomain contacts the 3' half of this site (ATGCAAAT), and the docking is similar to that of the engrailed, MAT alpha 2, and Antennapedia homeodomains. The linker region is not visible and there are no protein-protein contacts between the domains, but overlapping phosphate contacts near the center of the octamer site may favor cooperative binding. This novel arrangement raises important questions about cooperativity in protein-DNA recognition.

Amino Acid Sequence↗
PubMed1993

The solution structure of the Oct-1 POU-specific domain reveals a striking similarity to the bacteriophage lambda repressor DNA-binding domain.

The POU-specific (POUs) domain, in association with a POU-type homeodomain, forms the bipartite DNA-binding POU domain. The solution structure of the Oct-1 POUs domain has been determined by multidimensional nuclear magnetic resonance spectroscopy and consists of four alpha helices surrounding a conserved hydrophobic core. The POUs domain is structurally similar to the DNA-binding domains of the bacteriophage lambda and 434 repressors and 434 Cro. These domains exhibit superimposable helix-turn-helix (HTH) motifs, except that in the POUs domain, the first helix and the linker to the second helix of the motif are extended. The conserved structural features have been used to propose a plausible model for DNA binding by the POUs domain. A human dwarfism mutation that affects positive control in the related POU domain protein Pit-1 maps to the same region of the HTH motif as do positive control mutations in lambda repressor.

Amino Acid Sequence↗
PubMed1992

Segments of the POU domain influence one another's DNA-binding specificity.

The ubiquitously expressed mammalian POU-domain protein Oct-1 specifically recognizes two classes of cis-acting regulatory elements that bear little sequence similarity, the octamer motif ATGCAAAT and the TAATGARAT motif. The related pituitary-specific POU protein Pit-1 also recognizes these two motifs but, unlike Oct-1, binds preferentially to the TAATGARAT motif. Yet in our assay, Pit-1 still binds octamer elements better than does the octamer motif-binding protein Oct-3. The POU domain is responsible for recognizing these diverse regulatory sequences through multiple DNA contacts that include the two POU subdomains, the POU-specific region, and the POU homeodomain. The DNA-binding properties of 10 chimeric POU domains, in which different POU-domain segments are derived from either Oct-1 or Pit-1, reveal a high degree of structural plasticity; these hybrid proteins all bind DNA well and frequently bind particular sites better than does either of the parental POU domains. In these chimeric POU domains, the POU-specific A and B boxes and the hypervariable POU linker can influence DNA-binding specificity. The surprising result is that the influence a particular segment has on DNA-binding specificity can be greatly affected by the origin of other segments of the POU domain and the sequence of the binding site. Thus, the broad but selective DNA-binding specificity of Oct-1 is conferred both by multiple DNA contacts and by dynamic interactions within the DNA-bound POU domain.

Amino Acid Sequence↗