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S Sri Krishna

Publications and source records attributed to S Sri Krishna.

22 records · Page 2Linked to original sources
PubMed2004

A zinc-binding dual-specificity YVH1 phosphatase in the malaria parasite, Plasmodium falciparum, and its interaction with the nuclear protein, pescadillo.

Biochemical evidence revealed protein tyrosine kinase and phosphatase activities in the human malarial parasite Plasmodium falciparum, a member of the Apicomplexa. A novel cDNA sequence of a dual-specificity phosphatase was identified in both sexual and asexual stages of P. falciparum, and named PfYVH1, since the predicted primary structure of the 278-amino acid polypeptide showed significant similarity to the human and yeast YVH1 phosphatases. The N-terminal half of PfYVH1 contained a conserved tyrosine phosphatase catalytic domain within a dual-specificity phosphatase domain. The C-terminal region, consisting of one histidine and eight cysteines, represented a zinc-binding domain with a potentially unconventional architecture. Recombinant PfYVH1 contained 2mol of zinc per mol protein and dephosphorylated both phosphoserine and phosphotyrosine residues. Mutation of specific Cys residues in the putative zinc finger region abolished zinc binding and drastically reduced phosphatase activity, suggesting an allosteric role of zinc in catalysis. PfYVH1 was expressed in essentially all erythrocytic stages of the parasite, and shuttled between the nucleus and the cytoplasm in a stage-specific manner. A Plasmodium ortholog of the nuclear pescadillo protein (PfPES) was also characterized and shown to interact with PfYVH1, thus implicating PfYVH1 in the regulation of parasitic development. PfYVH1 represents the first dual-specificity zinc-finger phosphatase characterized in the protozoan kingdom.

Amino Acid Sequence↗
PubMed2003

Structural classification of zinc fingers: survey and summary.

Zinc fingers are small protein domains in which zinc plays a structural role contributing to the stability of the domain. Zinc fingers are structurally diverse and are present among proteins that perform a broad range of functions in various cellular processes, such as replication and repair, transcription and translation, metabolism and signaling, cell proliferation and apoptosis. Zinc fingers typically function as interaction modules and bind to a wide variety of compounds, such as nucleic acids, proteins and small molecules. Here we present a comprehensive classification of zinc finger spatial structures. We find that each available zinc finger structure can be placed into one of eight fold groups that we define based on the structural properties in the vicinity of the zinc-binding site. Three of these fold groups comprise the majority of zinc fingers, namely, C2H2-like finger, treble clef finger and the zinc ribbon. Evolutionary relatedness of proteins within fold groups is not implied, but each group is divided into families of potential homologs. We compare our classification to existing groupings of zinc fingers and find that we define more encompassing fold groups, which bring together proteins whose similarities have previously remained unappreciated. We analyze functional properties of different zinc fingers and overlay them onto our classification. The classification helps in understanding the relationship between the structure, function and evolutionary history of these domains. The results are available as an online database of zinc finger structures.

Algorithms↗
PubMed2003

CASP5 assessment of fold recognition target predictions.

We present an overview of the fifth round of Critical Assessment of Protein Structure Prediction (CASP5) fold recognition category. Prediction models were evaluated by using six different structural measures and four different alignment measures, and these scores were compared to those assigned manually over a diverse subset of target domains. Scores were combined to compare overall performance of participating groups and to estimate rank significance. The methods used by a few groups outperformed all other methods in terms of the evaluated criteria and could be considered state-of-the-art in structure prediction. We discuss a few examples of difficult fold recognition targets to highlight the progress of ab initio-type methods on difficult structure analogs and the difficulties of predicting multidomain targets and selecting prediction models. We also compared the results of manual groups to those of automatic servers evaluated in parallel by CAFASP, showing that the top performing automated server structure predictions approached those of the best manual predictors.

Algorithms↗