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Biomedical subjects

C Verma

Publications and source records attributed to C Verma.

28 records · Page 2Linked to original sources
PubMed1995

The structural origins of the unusual specificities observed in the isolation of chymopapain M and actinidin by covalent chromatography and the lack of inhibition of chymopapain M by cystatin.

1. The selectivity observed when the potentially general technique for the isolation of fully active forms of cysteine proteinases, covalent chromatography by thiol-disulphide interchange, is applied to chymopapain M and to actinidin was investigated by a combination of experimentation and computer modelling. Neither of these enzymes is able to react with the original Sepharose-GSH-2-dipyridyl disulphide gel, but fully active forms of both enzymes are obtained by using Sepharose-2-hydroxypropyl-2'-dipyridyl disulphide gel, which is both electrically neutral and sterically less demanding than the GSH gel. Electrostatic potential calculations, minimization and molecular-dynamics simulations provide explanations for the unusual, but different, specificities exhibited by actinidin and chymopapain M in the interactions of their active centres with ligands. 2. The unique behaviour of chymopapain M in exerting an almost absolute specificity for substrates with glycine at the P1 position and in resisting inhibition by cystatin was examined by the computer-modelling techniques. A new, modelled, structure of the complete chicken egg-white cystatin molecule based on the crystal structure of a short form of cystatin was deduced as a necessary prerequisite. The results suggest that electrostatic repulsion prevents reaction of actinidin with the GSH gel, whereas a steric 'cap' resulting from a unique arginine-65-glutamic acid-23 interaction in chymopapain M prevents reaction of the gel with this enzyme and accounts for the lack of its inhibition by cystatin and its specificity in catalysis. 3. Use of chymopapain M as a structural variant of papain demonstrates the validity of the predictions of Lowe and Yuthavong [Biochem. J. (1971) 124, 107-115] relating to the structural requirements and binding characteristics of the S1 subsite of papain.

Binding Sites↗
PubMed1994

Probing the nature of substrate binding in Humicola lanuginosa lipase through X-ray crystallography and intuitive modelling.

The catalytic triad of the neutral lipase from Humicola lanuginosa is buried by a short helix under aqueous conditions rendering the enzyme inactive. Upon adsorption to a lipid substrate interface this helix is displaced, thereby exposing the active site (interfacial activation). By covalently linking inhibitors to the active serine, it is possible to crystallize the enzyme in an interfacially activated state. Two such structures are reported here which mimic the tetrahedral transition states of lipolysis. To date, no crystal structures of a lipase--triglyceride complex exist for this enzyme. Therefore, possible interactions between this lipase and its substrate have been analysed through molecular modelling.

Binding Sites↗
PubMed1989

Prevalence of haemoglobin D in Uttar Pradesh.

Haemolysates from 1098 unrelated individuals residing at Lucknow were investigated for haemoglobin variants by cellogel electrophoresis. Haemoglobin 'D' trait was found in 16 subjects (1.5%). The prevalence of Hb-D trait in Khatris was 3.1 per cent compared to 0.5 per cent in other Hindus. One case of Hb-D trait with thaiassaemia was also seen in a Muslim girl.

Adolescent↗
PubMed1986

Electrotypes and formal genetics of red cell glutathione peroxidase (GPX1) in the Djuka of Surinam.

Samples of venous blood from 239 male and 476 female adults including 41 pairs of parents and 123 of their children belonging to a Surinam population called the Djuka or Bush Negroes of West African origin were screened for electrophoretic variants of red cell glutathione peroxidase (GPX1) in Cellogel. The results confirmed an earlier hypothesis that at least a part of the GPX1 variation mainly, if not exclusively, observed in the Africans and people of African origin living elsewhere, is determined by two codominant alleles (called GPX1*1 and GPX1*2), at an autosomal locus. The frequency of GPX1*2 allele in the Djuka was estimated to be .054. A rare variant provisionally designed as GPX1 Djuka (thought to be a heterozygote due to a third allele called GPX1*3 and the GPX1*1) was found in two apparently unrelated individuals. Catalytically, the product of GPX1*2 appears to be about twice more active than that of GPX1*1. For heuristic purposes, it was proposed and discussed that GPX1*2 is a South-Saharan African allele and is amenable for natural selection.

Adult↗
PubMed1984

Red cell glutathione peroxidase (GPX1) variation in Afro-Jamaican, Asiatic Indian, and Dutch populations. Is the GPX1*2 allele of "Thomas" variant an African marker?

A Cellogel procedure for screening the electrophoretic variants of the human red cell glutathione peroxidase ( GPX1 ) was described. Three hundred and ninety eight Dutch persons living in various parts of The Netherlands, 385 individuals born in various states of India, and 72 Jamaicans of African origin living in Birmingham, UK, were screened for GPX1 variants. The Dutch were monomorphic, while one Afro-Jamaican female and two males and one female of the 116 Punjabis were found to be variants indistinguishable from each other in their pattern of electrophoresis. The clear five banded pattern of the variant indicated that the subunit structure of the human red cell glutathione peroxidase is most probably a tetramer and suggested that the variant is the expression of a heterozygote due to alleles at an autosomal locus. The corresponding phenotype was designated tentatively as GPX1 2-1 and the alleles as GPX1 *1 and GPX1 *2 respectively. The variant 2-1 was found to be identical to the "Thomas" variant described by Beutler and West (1974). Thus so far, in addition to the Afro-Americans and Ashkenazi Jews (Beutler et al. 1974), the Punjabis of the Indian subcontinent (this report) were found to exhibit the GPX1 polymorphism due to the GPX1 *2 allele. The data discussed in this paper (which included unpublished observations on several African and non-African populations) suggest that the GPX1 *2 allele is originally an African variant and hint that the present day Punjabis of Indian subcontinent, like Ashkenazi Jews, are "predominantly of Mediterranean origin with some proportion of African ancestry" ( Mourant et al. 1976).

Black People↗