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J Echave

Publications and source records attributed to J Echave.

7 recordsLinked to original sources
PubMed2006

Sulfide-binding hemoglobins: Effects of mutations on active-site flexibility.

The dynamics of Hemoglobin I (HbI) from the clam Lucina pectinata, from wild-type sperm whale (SW) myoglobin, and from the L29F/H64Q/V68F triple mutant of SW, both unligated and bound to hydrogen sulfide (H2S), have been studied in molecular dynamics simulations. Features that account for differences in H2S affinity among the three have been examined. Our results verify the existence of an unusual heme rocking motion in unligated HbI that can promote the entrance of large ligands such as H2S. The FQF-mutant partially reproduces the amplitude and relative orientation of the motion of HbI's heme group. Therefore, besides introducing favorable electrostatic interactions with H2S, the three mutations in the distal pocket change the dynamic properties of the heme group. The active-site residues Gln-64(E7), Phe-43(CD1), and His-93(F8) are also shown to be more flexible in unligated HbI than in FQF-mutant and SW. Further contributions to H2S affinity come from differences in hydrogen bonding between the heme propionate groups and nearby amino acid residues.

Amino Acid Substitution↗
PubMed2001

Structural constraints and emergence of sequence patterns in protein evolution.

The aim of this work was to study the relationship between structure conservation and sequence divergence in protein evolution. To this end, we developed a model of structurally constrained protein evolution (SCPE) in which trial sequences, generated by random mutations at gene level, are selected against departure from a reference three-dimensional structure. Since at the mutational level SCPE is completely unbiased, any emergent sequence pattern will be due exclusively to structural constraints. In this first report, it is shown that SCPE correctly predicts the characteristic hexapeptide motif of the left-handed parallel beta helix (LbetaH) domain of UDP-N-acetylglucosamine acyltransferases (LpxA).

Acyltransferases↗
PubMed2000

Delay model of the circadian pacemaker.

We present a simple and realistic model of the circadian pacemaker that can be interpreted in molecular terms. The model, which consists of a single time-delay differential equation, simulates the expression of a generic clock protein that inhibits its own expression through a feedback mechanism. Despite its simplicity, this model fulfils most of the necessary characteristics of a realistic representation of natural circadian clocks: robust and stable oscillations with circadian free-running periods, typical phase response curves and entrainment to environmental zeitgebers. The present model reduces the molecular mechanism necessary to sustain stable oscillations to its bare bones, suggesting that the essential factor is the time-delayed negative feedback of the oscillating protein on its own expression.

Animals↗
PubMed2000

Evolutionary analysis of gamma-carbonic anhydrase and structurally related proteins.

We studied the evolutionary relationships between gamma-carbonic anhydrase (gamma-CA) and a very diverse group of proteins that share the sequence motif characteristic of the left-handed parallel beta-helix (LbetaH) fold. This sequence motif is characterized by the imperfect tandem repetition of short hexapeptide units, which makes it difficult to obtain a reliable alignment based on sequence information alone. To solve this problem, we used a structural alignment of three members of the group with known crystallographic structures as a seed to obtain a reliable sequence alignment. Then, we applied protein maximum-parsimony and maximum-likelihood phylogenetic inference methods to this alignment. We found that gamma-CA belongs to a diverse superfamily of proteins that share the LbetaH domain. This superfamily is composed mainly of acyltransferases. The most remarkable feature of the phylogenetic tree obtained is that its main branches group together functionally related proteins, so that the coarse topology can be rather easily explained in terms of functional diversification. Regarding the main branch of the tree containing gamma-CA, we found that, in addition to the group of its closest relatives that had already been studied, gamma-CA is closely related to the tetrahydrodipicolinate N-succinyltransferases.

Acyltransferases↗
PubMed1996

Computational characterisation of potential RNA-binding sites in arenavirus nucleocapsid proteins.

A nucleocapsid protein of an RNA virus was characterised using computational methods. Similarity searches using standard algorithms and more sensitive methods based on profiles were performed. Also, secondary structure prediction and statistical methods were used. The results show that the protein belongs to a unique well-characterised family, with three regions with potential RNA binding capacity. The amino-terminal region is found to contain a mixed-charge segment similar to proteins that bear nucleic acid-protein interaction capacity. The middle-region has a slight homology to the nucleolar protein Fibrillarin containing an atypical RNP-1 conserved octamer. Finally, the carboxyl-terminal region has a putative zinc-finger.

Algorithms↗
PubMed1996

Rapid automated determination of adenosine deaminase and lysozyme for differentiating tuberculous and nontuberculous pleural effusions.

The catalytic concentration of pleural adenosine deaminase (ADA) and the ratio of pleural lysozyme (PL) to serum lysozyme (SL) were measured in consecutive patients (49 tuberculous and 179 nontuberculous) with two automated procedures in a Hitachi 717 analyzer. Using sensitivity and specificity curves, we established cutoff values at 33 U/L for ADA and 1.7 for the PL/SL ratio. The sensitivity of ADA activities for tuberculous effusion was 90%, specificity 85%. Combining ADA with the PL/SL ratio enhanced specificity to 99%. However, high values for ADA and lysozyme ratios are not, alone or in combination, sensitive or specific enough to replace pleural biopsy or culture of pleural fluid for the diagnosis of tuberculous empyema.

Adenosine Deaminase↗