Biomedical subjects

G Baudoux

Publications and source records attributed to G Baudoux.

4 recordsLinked to original sources

PubMed1998

First partial three-dimensional model of human monoamine oxidase A.

A survey of the major known structural aspects of monoamine oxidase (MAO) is given and a first partial model of human MAO A is presented. This 3D model has been established using secondary structure predictions and fold recognition methods. It shows two alpha/beta domains (the FAD-binding N-terminal and central domains) and an alpha+beta domain. The C-terminal region is predicted to be responsible for anchoring the protein into the mitochondrial membrane and was not modeled. The covalent binding of the flavin cofactor to a cysteine residue is well predicted. The model is validated with experimental data from the literature and should be useful in designing new experimental studies (site-directed mutagenesis, chemical modification, specific antibodies). This first step towards the 3D structure of monoamine oxidase should contribute to a better understanding of the mechanisms of action and inhibition of this drug target in the treatment of clinical depression.

Amino Acid Sequence↗

PubMed1998

Comparative analysis of seven multiple protein sequence alignment servers: clues to enhance reliability of predictions.

MOTIVATION: The prediction reliability of seven multiple alignment servers currently available on the Internet (ClustalW, MAP, PIMA, Block Maker, MSA, MEME and Match-Box) has been evaluated in terms of power (sensitivity) and confidence (selectivity). Therefore, the alignments obtained have been respectively compared to refined structural alignments for 20 families of related proteins with low levels of identity. RESULTS: Results clearly show that any powerful method remains reliable when the rate of identity falls. For some methods, power and confidence decrease linearly with the rate of identity, while other methods emphasize reliability at the cost of a lower power. Increasing the number of related sequences included in the alignment may either improve or decrease the quality of the predictions substantially. For some methods, the gain in power or in confidence is quite systematic; for others, the effect of the addition of homologous sequences is highly unpredictable. Extracting the consensus between two different methods may increase the overall confidence of the predictions tremendously. Our conclusions induce users of sequence alignment methods on the Internet to select the most suitable technique according to their requirements in terms of selectivity and sensitivity. AVAILABILITY: The aligned sequences of the 20 alignments of structure can be obtained automatically by sending the message 'send: cabios_tests.txt' by e-mail to 'matchbox@biq.fundp.ac.be'. CONTACT: eric.depiereux@fundp.ac.be

Computer Communication Networks↗

PubMed1997

Match-Box_server: a multiple sequence alignment tool placing emphasis on reliability.

MOTIVATION: The Match-Box software comprises protein sequence alignment tools based on strict statistical thresholds of similarity between protein segments. The method circumvents the gap penalty requirement: gaps being the result of the alignment and not a governing parameter of the procedure. The reliable conserved regions outlined by Match-Box are particularly relevant for homology modelling of protein structures, prediction of essential residues for site-directed mutagenesis and oligonucleotide design for cloning homologous genes by polymerase chain reaction (PCR). RESULTS: The method produces reliable results, as assessed by tests performed on protein families of known structures and of low sequence similarity. A reliability score is computed in relation to a threshold of similarity progressively raised to extend the aligned regions to their maximal length, up to the significance limit of matching segments. The score obtained at each position is printed below the sequences and allows a discriminant reading of each aligned region. AVAILABILITY: Sequences may be submitted to a Web server at http://www.fundp.ac.be/sciences/biologie/bms/+ ++matchbox_submit.html or sent by e-mail to matchbox/biq.fundp.ac.be (help available by just mailing help).

Algorithms↗

PubMed1996

Recovery potential in glucose deprived astrocytes.

D-glucose deprivation for a 45 min period reduces the ATP and creatine phosphate concentrations of astrocytes. Recovery experiments were initiated by reincubating the cells with D-glucose and glucose replacement metabolites. No recovery of ATP concentration could be obtained even after 1 h of reincubation with the replacement metabolites. After a 45 min incubation period without D-glucose, 14CO2 production fell to 36% and 21% of controls when the cells were reincubated respectively with D-[U-14C]-glucose and L-[2-14C]-pyruvate as substrate marker. When reincubated for 1 h in the presence of L-malate (1 mM)+L-pyruvate (10 mM) with L-[2-14C]-pyruvate as marker, a total recovery of 14CO2 production was ascertained. Reincubation of the glucose deprived cells in the presence of D-glucose (10 mM) did not increase the 14CO2 production indicating that the cells were unable to use D-glucose for oxidative purposes. As pyruvate concentration was dramatically decreased in glucose deprived cells, astrocytes were treated with alpha-ketovalerate (25 mM) which led to an 8-fold increase in pyruvate concentration. In these conditions 14CO2 production did not increase when the cells were incubated in the presence of L-malate (1 mM). O2 consumption of State 4 in astrocytes, submitted to glucose deprivation, decreased. These cells treated with FCCP could not be uncoupled and when reincubated in the presence of replacement metabolites only a 20% increase of oxygen consumption took place.

Adenosine Triphosphate↗