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Titolo:
Substrate specificity of recombinant cysteine proteinase, CPB, of Leishmania mexicana
Autore:
Alves, LC; Judice, WAS; St Hilaire, PM; Meldal, M; Sanderson, SJ; Mottram, JC; Coombs, GH; Juliano, L; Juliano, MA;
Indirizzi:
Univ Fed Sao Paulo, Escola Paulista Med, Dept Biophys, BR-04044020 Sao Paulo, Brazil Univ Fed Sao Paulo Sao Paulo Brazil BR-04044020 BC4020 Sao Paulo, Brazil Carlsberg Lab, Dept Chem, DK-2500 Valby, Denmark Carlsberg Lab Valby Denmark DK-2500 b, Dept Chem, DK-2500 Valby, Denmark Univ Glasgow, Inst Biomed & Life Sci, Div Infect & Immun, Glasgow G12 8QQ,Lanark, Scotland Univ Glasgow Glasgow Lanark Scotland G12 8QQ gow G12 8QQ,Lanark, Scotland Univ Glasgow, Anderson Coll, Wellcome Ctr Mol Parasitol, Glasgow G11 6NU, Lanark, Scotland Univ Glasgow Glasgow Lanark Scotland G11 6NU ow G11 6NU, Lanark, Scotland
Titolo Testata:
MOLECULAR AND BIOCHEMICAL PARASITOLOGY
fascicolo: 1, volume: 116, anno: 2001,
pagine: 1 - 9
SICI:
0166-6851(200108)116:1<1:SSORCP>2.0.ZU;2-6
Fonte:
ISI
Lingua:
ENG
Soggetto:
HOST-CELL INVASION; TRYPANOSOMA-CRUZI; PROTEASE INHIBITORS; PARASITIC DISEASES; CATHEPSIN-B; GENE ARRAY; PROMASTIGOTES; AMASTIGOTES; GP57/51; IDENTIFICATION;
Keywords:
thiol protease; cysteine proteinase; Leishmania; inhibitors; cathepsin L; cruzain;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
46
Recensione:
Indirizzi per estratti:
Indirizzo: Juliano, MA Univ Fed Sao Paulo, Escola Paulista Med, Dept Biophys, Rua Tres de Maio 100, BR-04044020 Sao Paulo, Brazil Univ Fed Sao Paulo Rua Tres deMaio 100 Sao Paulo Brazil BR-04044020 BC
Citazione:
L.C. Alves et al., "Substrate specificity of recombinant cysteine proteinase, CPB, of Leishmania mexicana", MOL BIOCH P, 116(1), 2001, pp. 1-9

Abstract

The primary S-1 subsite specificity of a recombinant cysteine, proteinase,CPB2.8 Delta CTE, of Leishmania mexicana was investigated in a systematic way using a series of peptides derived from Abz-KLRFSKQ-EDDnp in which Arg was substituted by all natural amino acids (where Abz is oi-tho-amino-benzoyl and EDDnp is N-[2,4-dinitrophenyl]-ethylenediamine). The peptides from this series with charged side chain amino acids, Cys, Cys(SBzl), and Thr(OBzl) were well hydrolysed. All other substitutions resulted in peptides that were resistant or hydrolysed very slowly and inhibited the enzyme with Ki values in the range of 9-400 nM. Looking for natural substrates for CPB2.8, we observed that the recombinant enzyme failed to release kinin from human kininogen, an activity earlier observed with cruzipain from Trypanosoma cruzi (Del Nery et al., J. Biol. Chem. 272 (1997) 25713.). This lack of activity seems to be a result of the resistance to hydrolysis of the sequence at the N-terminal site of bradykinin in the human kininogen. The preferences for the S-3, S-2 and S-1' -S-3' for some amino acids were also examined using substrates derived from Abz-KLRFSKQ-EDDnp with variations at Lys, Leu, Phe, Ser and Lys, using the amino acids Ala, Phe, Leu, His or Pro. Peptides with Phe at P-1' presented the highest affinity to the leishmanial enzyme. For comparison, some of the obtained peptides were also assayed with recombinant human cathepsin L and cruzain. The best substrates for CPB2.8 Delta CTE were also well hydrolysed by cathepsin L, however, the best inhibitors ofthe parasite enzyme have low affinity to cathepsin L. These promising dataprovide leads for the design of anti-parasitic drugs directed against the leishmanial enzyme. (C) 2001 Elsevier Science B.V. All rights reserved.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 08/07/20 alle ore 07:46:03