Bestatin-mediated inhibition of leucine aminopeptidase may hinder HIV infection

Pulido-Cejudo, Gabriel; Conway, Brian; Proulx, Pierre; Brown, Robert; Izaguirre, Carlos A.

doi:10.1016/s0166-3542(97)00052-1

Cited by 75 publications

(62 citation statements)

References 22 publications

(29 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…They are necessary for proper functioning of eukaryotic and prokaryotic cells, but often are also important factors in various pathological states and diseases such as: malaria, cancer, diabetes, HIV, cataracts, angiogenesis, hypertension, systemic lupus (Hooper and Lendeckel 2004;Sanderink et al 1988;Sanz 2007;Jankiewicz and Bielawski 2003;Pulido-Cejudo et al 1997;Taylor et al 1982;Sharma et al 1996;Inokuma et al 1999;Umezawa 1980;Pretlow et al 1994;Mathe 1991).…”

Section: Introductionmentioning

confidence: 99%

The influence of α-aminophosphonic acids on the activity of aminopeptidase from barley seeds—an approach to determine the enzyme specificity

2015

View full text Add to dashboard Cite

Inhibitory potencies of 24 a-aminophosphonic acids against barley seeds (Hordeum vulgare L.) metalloaminopeptidase have been determined to evaluate structural requirements of this enzyme. The enzyme was sensitive mostly to the influence of phosphonic acid analogues of phenylalanine and its homologues, thus showing narrow specificity if compared with porcine aminopeptidases M1 and M17 and with Plasmodium aminopeptidase M17.

show abstract

Section: Introductionmentioning

confidence: 99%

The influence of α-aminophosphonic acids on the activity of aminopeptidase from barley seeds—an approach to determine the enzyme specificity

2015

View full text Add to dashboard Cite

show abstract

“…There is also mounting evidence that N-acetylaspartylglutamate is involved in neuropsychiatric disorders associated with the dysregulation of glutamatergic neurotransmission, such as schizophrenia, seizure disorders, Parkinson's disease, and amyotrophic lateral sclerosis (15). For this reason, these metallohydrolases have become the subject of intense efforts in inhibitor design (16).…”

mentioning

confidence: 99%

The Catalytic Role of Glutamate 151 in the Leucine Aminopeptidase from Aeromonas proteolytica

Bzymek

Holz

2004

Journal of Biological Chemistry

View full text Add to dashboard Cite

Glutamate 151 has been proposed to act as the general acid/base during the peptide hydrolysis reaction catalyzed by the co-catalytic metallohydrolase from Aeromonas proteolytica (AAP). However, to date, no direct evidence has been reported for the role of Glu-151 during catalytic turnover by AAP. In order to elucidate the catalytic role of Glu-151, altered AAP enzymes have been prepared in which Glu-151 has been substituted with a glutamine, an alanine, and an aspartate. The Michaelis constant (K m ) does not change upon substitution to aspartate or glutamine, but the rate of the reaction changes drastically in the following order: glutamate (100% activity), aspartate (0.05%), glutamine (0.004%), and alanine (0%). Examination of the pH dependence of the kinetic constants k cat and K m revealed a change in the pK a of a group that ionizes at pH 4.8 in recombinant leucine aminopeptidase (rAAP) to 4.2 for E151D-AAP. The remaining pK a values at 5.2, 7.5, and 9.9 do not change. Proton inventory studies indicate that one proton is transferred in the rate-limiting step of the reaction at pH 10.50 for both rAAP and E151D-AAP, but at pH 6.50 two protons and general solvation effects are responsible for the observed effects in the reaction catalyzed by rAAP and E151D-AAP, respectively. Based on these data, Glu-151 is intrinsically involved in the peptide hydrolysis reaction catalyzed by AAP and can be assigned the role of a general acid and base.

show abstract

“…A lot of clinical trials confirmed that bestatin in combination with chemotherapy prolongs both the remission period and survival time of patients with leukemia (Ota and Uzuka 1992, Urabe et al 1993, Hirayama et al 2003. There are also interesting and promising evidences that bestatin has an adjuvant effect on a DNA AIDS vaccine (Sasaki et al 1998) and may hinder HIV infection (Pulido-Cejudo et al 1997).…”

Section: Introductionmentioning

confidence: 99%

Influence of bestatin, an inhibitor of aminopeptidases, on T and B lymphocyte subsets in mice

Lis¹,

Szczypka²,

Suszko³

et al. 2011

Polish Journal of Veterinary Sciences

View full text Add to dashboard Cite

Bestatin, a low-molecular weight dipeptide, is a potent inhibitor of aminopeptidase N which has been demonstrated to have antitumor and immunomodulatory effects. The effects of bestatin (10, 1 and 0.1mg/kg) administered intraperitoneally once, five or ten times to mice on the total number of lymphocytes in the thymus, spleen and mesenteric lymph nodes and the percentage and the absolute number of T cell subsets (CD4 ) lymphocytes in the spleen and mesenteric lymph nodes were studied. It has been found that bestatin administered ten times at doses of 10, 1 and 0.1 mg/kg increased the total number of thymocytes, splenocytes and lymphocytes of mesenteric lymph nodes. Bestatin also changed the percentage and the absolute number of T cell subsets in the thymus and T and B lymphocytes in the peripheral lymphatic organs. Five and ten exposures to bestatin (10, 1 and 0.1 mg/kg) increased the absolute count of both immature CD4 + CD8 + and CD4 -CD8 -thymic cells. Moreover, both a single and multiple administration of bestatin (1 and 0.1 mg/kg) decreased the percentage and absolute count of CD3 + splenocytes and mesenteric lymph node cells with corresponding decreases in the percentage and absolute count of CD4 + and CD8 + cells. Both a single and multiple administration of bestatin at all the doses under investigation augmented the percentage and the absolute count of CD19 + (B lymphocytes) in the peripheral lymphatic organs. The results of the study show that there is a relationship between the effect induced by bestatin and the dose of the drug as well as the number of doses applied. The strongest effect on the T and B lymphocyte subsets was noted after five injections of bestatin at doses of 1 and 0.1 mg/kg.

show abstract

Bestatin-mediated inhibition of leucine aminopeptidase may hinder HIV infection

Cited by 75 publications

References 22 publications

The influence of α-aminophosphonic acids on the activity of aminopeptidase from barley seeds—an approach to determine the enzyme specificity

The influence of α-aminophosphonic acids on the activity of aminopeptidase from barley seeds—an approach to determine the enzyme specificity

The Catalytic Role of Glutamate 151 in the Leucine Aminopeptidase from Aeromonas proteolytica

Influence of bestatin, an inhibitor of aminopeptidases, on T and B lymphocyte subsets in mice

Contact Info

Product

Resources

About