Molecular modelling and dynamics of CA2 missense mutations causative to carbonic anhydrase 2 deficiency syndrome

Abstract

Carbonic anhydrase 2 (CA2) enzyme deficiency caused by CA2 gene mutations is an inherited disorder characterized by symptoms like osteopetrosis, renal tubular acidosis, and cerebral calcification. This study has collected the CA2 deficiency causal missense mutations and assessed their pathogenicity using diverse computational programs. The 3D protein models for all missense mutations were built, and analyzed for structural divergence, protein stability, and molecular dynamics properties. We found M-CAP as the most sensitive prediction method to measure the deleterious potential of CA2 missense mutations. Free energy dynamics of tertiary structure models of CA2 mutants with DUET, mCSM, and SDM based consensus methods predicted only 50% of the variants as destabilizing. Superimposition of native and mutant CA2 models revealed the minor structural fluctuations at the amino acid residue level but not at the whole protein structure level. Near native molecular dynamic simulation analysis indicated that CA2 causative missense variants result in residue level fluctuation pattern in the protein structure. This study expands the understanding of genotype-protein phenotype correlations underlying CA2 variant pathogenicity and presents a potential avenue for modifying the CA2 deficiency by targeting biophysical structural features of CA2 protein.

Communicated by Ramaswamy H. Sarma     

Impact of Habitat Fragmentation on the Demography of Lion-tailed Macaque (<Emphasis Type="Italic">Macaca silenus</Emphasis>) Populations in the Rainforests of Anamalai Hills,Western Ghats,India

Habitat fragmentation is considered the most serious threat to primate conservation in the tropics, and understanding it effects on lion-tailed macaque is very important because most of the populations live in fragmented habitats. We examined demographic parameters of 9 lion-tailed macaque groups in 8 rain forest fragments with reference to fragment area, tree density, canopy cover, tree height, and total basal area of food trees. Group size ranged from 7 to 90 individuals but was not related to habitat variables. Birth and growth rates of groups did not differ significantly between small (n = 4) and large (n = 4) fragments. Tree density, canopy cover, and total basal of food trees all show strong positive correlations with fragment area. Growth rate correlates with tree density, but there are no other significant relationships between birth or growth rate and habitat variables. The percentage of immature individuals in the group is significantly positively associated with the total basal area of food trees, but not with any other habitat variable. Comparison of our data from this study with data available for the same population in 1996 indicates a slight decline in birth rate but an increase in total number of individuals, from 154 to 242. Of the 5 small fragment groups, 3 have increased in size since 1996 while the sizes of the other 2 groups have remained the same. Based on this study, we advocate that to manage the fragile lion-tailed macaque groups the following steps need to be taken: 1) create dispersal corridors between the fragments using fruit trees to facilitate male dispersal, 2) construct canopy bridges across the prevailing roads, 3) protect the fragments from further degradation, and 4) periodically monitor these populations for long-term conservation.     

Proteomic profiling of L-cysteine induced selenite resistance in Enterobacter sp. YSU

Background  

Enterobacter sp. YSU is resistant to several different heavy metal salts, including selenite. A previous study using M-9 minimal medium showed that when the selenite concentration was 100,000 times higher than the sulfate concentration, selenite entered Escherichia coli cells using two pathways: a specific and a non-specific pathway. In the specific pathway, selenite entered the cells through a yet to be characterized channel dedicated for selenite. In the non-specific pathway, selenite entered the cells through a sulfate permease channel. Addition of L-cystine, an L-cysteine dimer, appeared to indirectly decrease selenite import into the cell through the non-specific pathway. However, it did not affect the level of selenite transport into the cell through the specific pathway.     

Simultaneous Cellulase Production, Saccharification and Detoxification Using Dilute Acid Hydrolysate of S. spontaneum with Trichoderma reesei NCIM 992 and Aspergillus niger

Bioethanol production from lignocellulosic materials has several limitations. One aspect is the high production cost of cellulases used for saccharification of substrate and inhibition of fermenting yeast due to inhibitors released in acid hydrolysis. In the present work we have made an attempt to achieve simultaneous cellulases production, saccharification and detoxification using dilute acid hydrolysate of Saccharum spontaneum with and without addition of nutrients, supplemented with acid hydrolyzed biomass prior to inoculation in one set and after 3 days of inoculation in another set. Organisms used were T. reesei NCIM 992, and Aspergillus niger isolated in our laboratory. Cellulase yield obtained was 0.8 IU/ml on fourth day with T. reesei. Sugars were found to increase from fourth to fifth day, when hydrolysate was supplemented with nutrients and acid hydrolyzed biomass followed by inoculation with T. reesei. Phenolics were also found to decrease by 67%.