Biomedical subjects

N Srinivasan

Publications and source records attributed to N Srinivasan.

At least 19 recordsLinked to original sources

PubMed2005

Interaction preferences across protein-protein interfaces of obligatory and non-obligatory components are different.

BACKGROUND: A polypeptide chain of a protein-protein complex is said to be obligatory if it is bound to another chain throughout its functional lifetime. Such a chain might not adopt the native fold in the unbound form. A non-obligatory polypeptide chain associates with another chain and dissociates upon molecular stimulus. Although conformational changes at the interaction interface are expected, the overall 3-D structure of the non-obligatory chain is unaltered. The present study focuses on protein-protein complexes to understand further the differences between obligatory and non-obligatory interfaces. RESULTS: A non-obligatory chain in a complex of known 3-D structure is recognized by its stable existence with same fold in the bound and unbound forms. On the contrary, an obligatory chain is detected by its existence only in the bound form with no evidence for the native-like fold of the chain in the unbound form. Various interfacial properties of a large number of complexes of known 3-D structures thus classified are comparatively analyzed with an aim to identify structural descriptors that distinguish these two types of interfaces. We report that the interaction patterns across the interfaces of obligatory and non-obligatory components are different and contacts made by obligatory chains are predominantly non-polar. The obligatory chains have a higher number of contacts per interface (20 +/- 14 contacts per interface) than non-obligatory chains (13 +/- 6 contacts per interface). The involvement of main chain atoms is higher in the case of obligatory chains (16.9 %) compared to non-obligatory chains (11.2 %). The beta-sheet formation across the subunits is observed only among obligatory protein chains in the dataset. Apart from these, other features like residue preferences and interface area produce marginal differences and they may be considered collectively while distinguishing the two types of interfaces. CONCLUSION: These results can be useful in distinguishing the two types of interfaces observed in structures determined in large-scale in the structural genomics initiatives, especially for those multi-component protein assemblies for which the biochemical characterization is incomplete.

Animals↗

PubMed2004

SUPFAM: a database of sequence superfamilies of protein domains.

BACKGROUND: SUPFAM database is a compilation of superfamily relationships between protein domain families of either known or unknown 3-D structure. In SUPFAM, sequence families from Pfam and structural families from SCOP are associated, using profile matching, to result in sequence superfamilies of known structure. Subsequently all-against-all family profile matches are made to deduce a list of new potential superfamilies of yet unknown structure. DESCRIPTION: The current version of SUPFAM (release 1.4) corresponds to significant enhancements and major developments compared to the earlier and basic version. In the present version we have used RPS-BLAST, which is robust and sensitive, for profile matching. The reliability of connections between protein families is ensured better than before by use of benchmarked criteria involving strict e-value cut-off and a minimal alignment length condition. An e-value based indication of reliability of connections is now presented in the database. Web access to a RPS-BLAST-based tool to associate a query sequence to one of the family profiles in SUPFAM is available with the current release. In terms of the scientific content the present release of SUPFAM is entirely reorganized with the use of 6190 Pfam families and 2317 structural families derived from SCOP. Due to a steep increase in the number of sequence and structural families used in SUPFAM the details of scientific content in the present release are almost entirely complementary to previous basic version. Of the 2286 families, we could relate 245 Pfam families with apparently no structural information to families of known 3-D structures, thus resulting in the identification of new families in the existing superfamilies. Using the profiles of 3904 Pfam families of yet unknown structure, an all-against-all comparison involving sequence-profile match resulted in clustering of 96 Pfam families into 39 new potential superfamilies. CONCLUSION: SUPFAM presents many non-trivial superfamily relationships of sequence families involved in a variety of functions and hence the information content is of interest to a wide scientific community. The grouping of related proteins without a known structure in SUPFAM is useful in identifying priority targets for structural genomics initiatives and in the assignment of putative functions. Database URL: http://pauling.mbu.iisc.ernet.in/~supfam.

Amino Acid Sequence↗

PubMed1992

Orthogonal beta beta motifs in proteins.

A super-secondary structural motif comprising two orthogonally oriented beta-strands connected by short linking segments of less than or equal to 5 residues has been identified from a data set of 65 independent protein crystal structures. Of the 42 examples from 14 proteins, a vast majority have only a single residue as the linking element. Analysis of the conformational angles at the junction reveals that the recently described type VIII beta-turn occurs frequently at the connecting hinge, while the type II beta-turn is also fairly common.

Animals↗

PubMed1992

Influence of corticosterone acetate on the spleen in intact and ovariectomized rats.

Increasing evidence of the interaction of glucocorticoids and ovarian steroids prompted the current study. Effects of exogenously administered corticosterone acetate (3.5 mg/100 g b.w/day for one week) were examined on splenic nucleic acids, protein, lactate, and on lactate dehydrogenase (LDH) specific activity and its isozymes in ovariectomized and ovary-intact Wistar rats (65-75 days old). Ovariectomy resulted in no significant change in the parameters studied except DNA which increased significantly. The administration of corticosterone to these rats did not produce any remarkable change in the ovariectomy caused increase in splenic DNA content. Nevertheless, it decreased the ratio of heart type subunits (H)/muscle type subunits (M) [H/M] of LDH isozymes. In the case of ovary-intact rats, corticosterone produced an increase in the concentration of splenic lactate but a decrease in the H/M ratio. Exogenously administered corticosterone exerts selective synergistic interaction with ovarian hormones on splenic lactate. The specific activity of LDH and the concentrations of RNA and protein remained unchanged during the interaction between ovarian hormones and corticosterone.

Analysis of Variance↗

PubMed1992

Effects of prolactin and androgens on enzymes of carbohydrate metabolism in prostate of castrated bonnet monkeys Macaca radiata (Geoffroy).

Effects of prolactin (PRL), bromocriptine (Br), testosterone propionate (TP), dihydrotestosterone (DHT) and the combinations of these androgens with PRL/Br on the specific activities of caudal and cranial prostatic cellular enzymes involved in carbohydrate metabolism in castrated mature bonnet monkeys have been studied. Castration decreased all the enzymes studied such as hexokinase (HK), 6-phosphofructokinase (6-PFK), glyceraldehyde-3-phosphate dehydrogenase (G-3-PD), pyruvate kinase (PK), glucose-6-phosphate dehydrogenase (G-6-PD) and 6-phosphogluconate dehydrogenase (6-PGD) in the cranial and caudal prostates. PRL elevated the activities of all the enzymes above normal except G-3-PD of cranial lobe. In the caudal lobe, PRL brought back the activities of HK, PFK, PK, G-6-PD to normal and 6-PGD above normal except G-3-PD. TP/DHT treatment increased all the enzymes in both the lobes. PRL given along with TP/DHT further enhanced the androgen action with regard to HK, PK, G-6-PD and 6-PGD of cranial and PFK, G-3-PD, PK, G-6-PD and 6-PGD of caudal lobe. Br treatment did not produce any alteration of these enzymes in both the lobes. In the cranial lobe, during Br+TP/DHT treatment, the stimulating effects of androgen were unaffected on all the enzymes except PK. On the other hand in the caudal, the stimulatory effects of androgens were affected and the activities of HK, PFK, PK and 6-PGD were significantly decreased. The present results suggest that PRL has a direct as well as a synergistic action with androgens on enzymes of EMP and HMP shunt in the prostates of monkeys.

Androgens↗

PubMed1992

Interaction of androgens and prolactin on prostatic enzymes of the pyruvate-malate cycle involved in lipogenesis in castrated mature monkey, Macaca radiata.

Effects of androgens, prolactin (Prl) and bromocriptine (Br) on the specific activities of prostatic (caudal and cranial) enzymes of the pyruvate-malate cycle were studied in castrated mature bonnet monkeys. Castration decreased the activity of NADP+ isocitrate dehydrogenase (ICDH), ATP citrate lyase, malate dehydrogenase (MDH), malic enzyme and fatty acid synthase (FAS). Administration of testosterone propionate (TP)/dihydrotestosterone (DHT) increased the activities of all these enzymes in both lobes. Malate dehydrogenase maintained normal activity. Prl also had a stimulatory effect on the enzymes and was further enhanced when Prl was given in combination with TP/DHT. Unlike Prl, bromocriptine treatment inhibited all the enzymes in both lobes. Thus, prolactin was found to have a direct as well as a synergistic effect with androgens on enzymes of the pyruvate-malate cycle in the prostate of castrated mature monkeys.

ATP Citrate (pro-S)-Lyase↗

PubMed1991

Increased degradation of dermal collagen in diabetic rats.

The effect of alloxan induced diabetes on the dermal collagen content of albino rats was studied in relation to few lysosomal enzymes. Diabetes decreased the dermal collagen content. The specific activities of the lysosomal enzymes studied in the diabetic rat skin were elevated. It has been established that lysosomal enzymes degrade the connective tissue components. Thus, it may be suggested that the increase in the lysosomal enzymes studied should have facilitated the decrease in dermal collagen content of diabetic rats by increasing the degradation of dermal collagen.

Animals↗

PubMed1990

Conformations of disulfide bridges in proteins.

The conformational characteristics of disulfide bridges in proteins have been analyzed using a dataset of 22 protein structures, available at a resolution of less than or equal to 2.0 A, containing a total of 72 disulfide crosslinks. The parameters used in the analysis include (phi, psi) values at Cys residues, bridge dihedral angles chi ss, chi i1, chi j1, chi i2, and chi j2, the distances C alpha i-C alpha j and C beta i-C beta j between the C alpha and C beta atoms of Cys(i) and Cys(j). Eight families of bridge conformations with three or more occurrences have been identified on the basis of these stereochemical parameters. The most populated family corresponds to the "left handed spiral" identified earlier by Richardson [1981) Adv. Protein Chem. 34, 167-330). Disulfide bridging across antiparallel extended strands is observed in alpha-lytic protease, crambin, and beta-trypsin and this structure is shown to be very similar to those obtained in small cystine peptides. Solvent accessible surface area calculations show that the overwhelming majority of disulfide bridges are inaccessible to solvent.

Cystine↗

PubMed1990

Influence of prolactin, androgens and bromocriptine on seminal vesicular and prostatic adenosine triphosphatases in castrated adult monkeys Macaca radiata.

E ects of prolactin (PRL), bromocriptine (Br), testosterone propionate (TP), dihydrotestosterone (DHT) and the combinations of these androgens with PRL/Br on specific activities of adenosine triphosphatases (ATPases) of seminal vesicles and cranial and caudal prostates were studied in castrated adult bonnet monkeys. Castration decreased all ATPases (sodium/potassium, magnesium and calcium dependent) of seminal vesicles and both the lobes of prostate. PRL restored the normal activities of all ATPases in both the organs. Br given alone decreased all ATPases of prostate but caused no significant alteration, particularly calcium dependent ATPases of seminal vesicles and caudal prostate. TP/DHT replacement restored all ATPases of both the organs to the normal levels. PRL + TP/DHT further enhanced all the ATPases activities of all the regions studied. Br + TP/DHT decreased all ATPases but it did not produce any alteration in the calcium ATPases of seminal vesicles. The results suggest that prolactin facilitates membrane transport enzymes in the cranial and caudal prostate and seminal vesicles of adult castrated bonnet monkeys.

Adenosine Triphosphatases↗

PubMed1989

Stereochemical modeling of disulfide bridges. Criteria for introduction into proteins by site-directed mutagenesis.

A computer modeling procedure for assessing the stereochemical suitability of pairs of residues in proteins as potential sites for introduction of cystine disulfide crosslinks has been developed. Residue pairs with C alpha-C alpha distances of less than or equal to 6.5 A and C beta-C beta distances of less than or equal to 4.5 A are chosen for geometrical fixation of S atoms using the program MODIP. The stereochemistry of the modeled disulfides is evaluated using limits for the structural parameters of the various torsion angles and S-S bond length in the disulfide bridge. The ability of the procedure to correctly model disulfides has been checked with examples of cystine peptides of known crystal structures and 103 disulfide bridges from 25 available protein crystal structures determined at less than or equal to 2 A resolution. An analysis of results on three proteins with engineered disulfides, T4 lysozyme, dihydrofolate reductase and subtilisin, is presented. Two positions for the introduction of 'stereochemically optimal' disulfides are identified in subtilisin.

Disulfides↗

PubMed1989

Effect of corticosterone on epididymal lipids in pubertal rat.

Serum corticosterone excess was induced by the administration of corticosterone acetate to adrenal intact rats. Different lipid classes were studied in unwashed and washed (epididymal sperm and fluid free) caput and cauda epididymides. The unwashed caput epididymidis registered a significant decrease in total lipid, cholesterol and phospholipid while total glyceride glycerol and its fractions were not altered after corticosterone treatment. Among phospholipid fractions phosphatidyl inositol, choline and ethanolamine showed a significant decrease. Unlike the unwashed caput epididymidis, the washed caput region recorded a marked increase in total lipid, glyceride glycerol and its fractions. However, total lipid in the washed cauda region significantly increased and the increase was mainly due to triacyl glycerol. Though the phospholipid fractions phosphatidyl choline and ethanolamine showed an increase, the total phospholipid was not altered significantly. Serum testosterone and prolactin registered a significant decrease while gonadotropins were unaltered. On the withdrawal of corticosterone treatment, all the lipid classes turned to normalcy along with serum testosterone and prolactin. It is concluded that corticosterone excess favours lipid accumulation in the sperm free epididymal tissue and its influence on epididymis is region specific and reversible.

Animals↗

PubMed1989

Utilization behaviour patterns of Siddha clinics in Salem, Tamil Nadu.

In Tamil Nadu, indigenous Siddha medicine (SM) is officially recognized and extensively used. Yet very little research information or published material is available on the extent of utilization behaviour of Siddha medicine in urban settings. This study examines the current patterns of utilization and consumer behavioural characteristics of SM through a field-based questionnaire survey of a sample of 300 patients attending 15 Siddha clinics in Salem, Tamil Nadu. Four areas were investigated: Socio-economic characteristics of the users; utilization behaviour pattern of patients; reasons for choice of Siddha therapy; opinions, attitudes, perception and satisfaction of users regarding Siddha therapy. The survey points out there is an inverse relationship between the number of patients using SM and income, education and distance travelled. Various factors were cited in choosing SM-such as, effectiveness of treatment, social influences of a relative or friend. Survey indicates that both modern medicine and SM seem to act as supporting rather than as competitive systems in a setting like Salem. People tend to seek both the system in search of a permanent cure.

Adolescent↗

PubMed1989

Effects of prolactin and androgens on seminal vesicular lipids of castrated mature bonnet monkeys Macaca radiata.

Effects of prolactin (PRL), bromocriptine (Br), testosterone propionate (TP), dihydrotestosterone (DHT) and the combination of these androgens with PRL/Br on the total lipid, total cholesterol, total glyceride glycerols, total phospholipid and their fractions in seminal vesicles of castrated mature monkeys were studied. Glyceride glycerols formed the major portion (50%) of total lipids in normal monkeys. Cholesterol and phospholipids were of equal share (25%). Esterified cholesterol formed major share (75%) of total cholesterol. Diacyl glycerol was the major (60%) glyceride glycerol and phosphatidyl choline and ethanolamine were the major phospholipid classes. Except triacyl glycerol castration markedly decreased all the lipid classes. PRL restored normal free and esterified cholesterol and phosphatidyl inositol but Br invariably decreased all the lipid classes. TP/DHT treatment stimulated the free and esterified cholesterol more than the control; it restored the normal glyceride glycerols. Phosphatidyl inositol, choline and ethanolamine were stimulated by androgens and other phospholipid classes were brought to normal. Addition of PRL + TP/DHT markedly increased esterified cholesterol, phosphatidyl inositol, choline, ethanolamine and phosphatidic acid. In all these aspects, Br counteracted the effects of androgens and PRL.

Animals↗

PubMed1988

Effects of androgens, prolactin and bromocriptine on seminal vesicular enzymes of the pyruvate malate cycle involved in lipogenesis in castrated mature monkeys, Macaca radiata.

The interaction of androgens and prolactin, the major factors regulating the male accessory sex organs, on the specific activity of seminal vesicular enzymes of the pyruvate/malate cycle were studied in castrated mature monkeys. Castration decreased the activity of these enzymes, including NADP+ isocitrate dehydrogenase, ATP citrate lyase, malate dehydrogenase, malic enzyme and fatty acid synthase. Testosterone propionate (TP)/dihydrotestosterone given as replacement to castrates increased the activity of all these enzymes, except for malate dehydrogenase. Prolactin restored normal activity of ATP citrate lyase, malic enzyme and fatty acid synthase but not of isocitrate dehydrogenase and malate dehydrogenase (MDH). Prolactin had a specific control over MDH. Moreover, when prolactin was combined with androgens a further stimulatory influence was observed on fatty acid synthase activity. In order to prove the direct influence of prolactin on enzymes of the pyruvate/malate cycle, bromocriptine was administered and this inhibited all of the enzymes. Thus prolactin was found to have a direct, as well as a synergistic, action with androgens on enzymes of the pyruvate/malate cycle in the seminal vesicles of monkeys.

ATP Citrate (pro-S)-Lyase↗

PubMed1987

Interaction of sex steroids and prolactin on phosphatases, transaminases, and citric acid in the ventral prostate of male albino rats.

The interaction of androgens, testosterone propionate (TP), and dihydrotestosterone (DHT) with prolactin (PRL) and estradiol-17 beta (E2) on phosphatases, transaminases, and citric acid were studied in the ventral prostate of prepubertal and adult intact and castrated rats. None of the secretory products studied were affected by androgens or their combinations with E2/PRL in prepubertal rats except for the increase observed in organ weight and DNA content. However, in adults the hormonal combinations produced some significant changes. Among the secretory products, phosphatases, glutamate oxaloacetic transaminase (GOT), and citric acid increased significantly in adult rats after the administration of TP/DHT. Glutamate pyruvic transaminase (GPT) required PRL along with TP/DHT to show an appreciable increment in intact adult rats. The synergistic effect of PRL with androgens was observed in the adult ventral prostatic secretory acid phosphatase and citric acid. Unlike PRL, E2 in combination with androgens produced an antagonistic effect in intact adult rats, which was well pronounced in the case of prostatic weight, DNA content secretory acid phosphatase, and citric acid. None of the androgens or their combination with PRL produced any significant change in DNA content compared to intact controls.

Acid Phosphatase↗

PubMed1987

Conformation of glycyl residues in globular proteins.

Glycine is unique among the amino acids in view of its symmetric nature. While the overall distribution of glycyl residues in the (phi, psi) plane is near-symmetric, there can be certain preferences for the individual conformations. An analysis of the observed glycyl conformations in 70 proteins has been carried out to find the influence of residues adjoining the glycyl residues. For this purpose, the (phi, psi) plane has been divided into two regions: the region in which phi is negative and the region in which phi is positive. The analysis is done in terms of the number of conformations occurring in these regions. It has been found that while the overall percentage distribution of glycyl residues between the positive and the negative phi regions is 54:46, the distribution shows asymmetry when the examples are sorted out in terms of X-Gly and Gly-Y doublets. The asymmetry becomes more prominent when the data are sorted out into triplets X-Gly-Y. Using the available information, it has been possible to designate 25 triplets as P-predominant and 19 as N-predominant. An examination of P-predominant triplets for possible occurrence in beta-bends having one of the conformations in the positive phi region shows that only 25% are of this nature. Thus, the P-preference of P-predominant triplets is not an outcome of the bend formation alone and must be an inherent property of these triplets.

Amino Acid Sequence↗

PubMed1986

Role of thyroid on testicular lipids in prepubertal, pubertal and adult rats. I. Hyperthyroidism.

The influence of thyroxine-induced hyperthyroidism on testicular neutral and phospholipids was studied in prepubertal, pubertal and adult rats. Thyroxine treatment (25 micrograms/100 g body weight) for 1 month decreased testicular total lipids, total glyceride glycerols, total cholesterol and total phospholipids. Different classes of glyceride glycerol, cholesterol and phospholipid were also diminished due to thyroxine treatment. All classes of lipids returned to the euthyroid level after the withdrawal of thyroxine treatment. The data obtained in the present study suggest that thyroid hormones have a definite influence on testicular lipid metabolism in rats.

Aging↗

PubMed1986

Effect of high-fat diet on cholesterol distribution in plasma lipoproteins, cholesterol esterifying activity in leucocytes, and erythrocyte membrane components studied: importance of body weight.

Effects of isocaloric changes in dietary fat on plasma lipoproteins and lipids and enzymes of erythrocytes and leucocytes were assessed. Subjects with a higher Brocca index showed increase in total and LDL cholesterol, significant reduction in HDL cholesterol, and increased total cholesterol:HDL cholesterol ratio after high-fat diet consumption. Due to high-fat diet feeding, erythrocyte membrane and leucocyte cholesterol and phospholipid contents were increased, cholesterol:phospholipid molar ratio was elevated, and erythrocyte enzymes (G6PD and 6PGD) and leucocyte enzymes (CEH and CES) were elevated. Erythrocyte membrane glycoprotein components showed marked increase, indicating possible alterations of membrane surfaces. The metabolic alterations were reversed slowly after resumption of the normal (low-fat) diet. Body weight plays an important role in the alterations in major lipoprotein cholesterol contents in response to changes in dietary fat composition. Cellular changes indicate alterations in structure and function of blood cells due to high-fat diet feeding.

Adult↗