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A Srinivas

Publications and source records attributed to A Srinivas.

8 recordsLinked to original sources

Small substrate, big surprise: fold, function and phylogeny of dihydroxyacetone kinases.

Dihydroxyacetone (Dha) kinases are a family of sequence-conserved enzymes which utilize either ATP (in animals, plants and eubacteria) or phosphoenolpyruvate (PEP, in eubacteria) as their source of high-energy phosphate. The kinases consist of two domains/subunits: DhaK, which binds Dha covalently in hemiaminal linkage to the Nepsilon2 of a histidine, and DhaL, an eight-helix barrel that contains the nucleotide-binding site. The PEP-dependent kinases comprise a third subunit, DhaM, which rephosphorylates in situ the firmly bound ADP cofactor. DhaM serves as the shuttle for the transfer of phosphate from the bacterial PEP: carbohydrate phosphotransferase system (PTS) to the Dha kinase. The DhaL and DhaK subunits of the PEP-dependent Escherichia coli kinase act as coactivator and corepressor of DhaR, a transcription factor from the AAA(+) family of enhancerbinding proteins. In Gram-positive bacteria genes for homologs of DhaK and DhaL occur in operons for putative transcription factors of the TetR and DeoR families. Proteins with the Dha kinase fold can be classified into three families according to phylogeny and function: Dha kinases, DhaK and DhaL homologs (paralogs) associated with putative transcription regulators of the TetR and DeoR families, and proteins with a circularly permuted domain order that belong to the DegV family.

Citrobacter freundii↗

An adenylyl cyclase pseudogene in Mycobacterium tuberculosis has a functional ortholog in Mycobacterium avium.

A number of genes similar to mammalian Class III nucleotide cyclases are found in mycobacteria, and biochemical characterization of some of these proteins has indicated that they code for adenylyl cyclases, with properties similar to the mammalian enzymes. Our earlier bioinformatic analysis had predicted that the Rv1120c gene in Mycobacterium tuberculosis is a pseudogene, while analysis of the genome of Mycobacterium avium indicated the presence of a functional ortholog. We therefore cloned and expressed Rv1120c and its ortholog from M. avium, Ma1120, in Escherichia coli, and find that while the protein from M. tuberculosis is misfolded and found in inclusion bodies, Ma1120 is expressed to high levels as a functional adenylyl cyclase. Sequence analysis of Ma1120 indicates interesting variations in critical amino acids that are known to be important for catalytic activity. Ma1120 is maximally active in the presence of MnATP as substrate ((app)Km approximately 400 microM), and is inhibited by P-site inhibitors (IC50 of 2',5'-dideoxy-3'-adenosine triphosphate approximately 730 nM) and tyrphostins (IC50 approximately 36 microM) in a manner similar to the mammalian enzymes. This therefore represents the first Class III cyclase biochemically characterized from M. avium, and the absence of a functional ortholog in M. tuberculosis suggests a unique role for this enzyme in M. avium.

Adenylyl Cyclase Inhibitors↗

Spontaneous regression of large gastric carcinoid.

We report a female patient who presented with an epigastric lump proved on open biopsy to be a carcinoid tumor. She had raised serum glucagon level and increased excretion of 5-hydroxy indolacetic acid in the urine. She refused surgery and was followed up at 3 monthly intervals. At 6 months the tumor had decreased considerably in size. At one year it was no longer palpable and ultrasound examination clarified that there was no tumor. This was confirmed by the finding of normal levels of 5-HIAA in the urine.

Adult↗

Unruptured aneurysm of sinus of Valsalva: report of 2 cases.

2 cases of unruptured aneurysm of the sinus of Valsalva are presented. Both the patients had involvement of the right sinus of Valsalva. One of the patients had associated systemic lupus erythematosus (SLE). Such an association has not been described in the literature. Clinical, echocardiographic and the angiographic features have been discussed and literature reviewed.

Adult↗

Acute hemodynamic response to vasodilators in primary pulmonary hypertension.

Acute hemodynamic effects of high flow oxygen (O2) inhalation, sublingual isosorbide dinitrate (ISDN), intravenous aminophylline (AMN) and sublingual nifedipine (NIF) were studied in 32 patients with primary pulmonary hypertension (PPH). In 30 out of 32 patients the basal ratio of pulmonary to systemic vascular resistance (Rp/Rs) was > 0.5 (mean = 0.77 +/- 0.20). Oxygen caused significant decrease in the mean resistance ratio to 0.68 +/- 0.20 (p = 0.005). ISDN, AMN and NIF caused increase in the resistance ratio to 0.79 +/- 0.26; 0.78 +/- 0.26; and 0.80 +/- 0.23 respectively. O2, ISDN, AMN and NIF caused a fall of Rp/Rs in 21 (65.6%), 10 (31.2%), 10(31.2%) and 9(28.1%) patients respectively. Thus, of the four drugs tested high flow O2 inhalation resulted in fall of Rp/Rs in two thirds of patients whereas ISDN, AMN and NIF caused a mean rise in Rp/Rs. One third of patients did respond acutely to the latter three drugs. Acute hemodynamic studies are useful before prescribing vasodilators in patients with PPH since more of the commonly used drugs like ISDN, AMN, NIF could have detrimental hemodynamic responses in some patients. However, great caution should be exercised before performing hemodynamic study as the procedure has definite mortality and morbidity.

Administration, Sublingual↗