HEMOGLOBIN DEGRADATION IN THE HUMAN MALARIA PATHOGEN PLASMODIUM-FALCIPARUM - A CATABOLIC PATHWAY INITIATED BY A SPECIFIC ASPARTIC PROTEASE

被引:222
作者
GOLDBERG, DE
SLATER, AFG
BEAVIS, R
CHAIT, B
CERAMI, A
HENDERSON, GB
机构
[1] ROCKEFELLER UNIV,MED BIOCHEM LAB,NEW YORK,NY 10021
[2] ROCKEFELLER UNIV,MASS SPECTROMETRY & GASEOUS ION CHEM LAB,NEW YORK,NY 10021
关键词
D O I
10.1084/jem.173.4.961
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Hemoglobin is an important nutrient source for intraerythrocytic malaria organisms. Its catabolism occurs in an acidic digestive vacuole. Our previous studies suggested that an aspartic protease plays a key role in the degradative process. We have now isolated this enzyme and defined its role in the hemoglobinolytic pathway. Laser desorption mass spectrometry was used to analyze the proteolytic action of the purified protease. The enzyme has a remarkably stringent specificity towards native hemoglobin, making a single cleavage between alpha-33Phe and 34Leu. This scission is in the hemoglobin hinge region, unraveling the molecule and exposing other sites for proteolysis. The protease is inhibited by pepstatin and has NH2-terminal homology to mammalian aspartic proteases. Isolated digestive vacuoles make a pepstatin-inhibitable cleavage identical to that of the purified enzyme. The pivotal role of this aspartic hemoglobinase in initiating hemoglobin degradation in the malaria parasite digestive vacuoles is demonstrated.
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收藏
页码:961 / 969
页数:9
相关论文
共 47 条
[1]   FEEDING MECHANISM OF AVIAN MALARIAL PARASITES [J].
AIKAWA, M ;
HEPLER, PK ;
HUFF, CG ;
SPRINZ, H .
JOURNAL OF CELL BIOLOGY, 1966, 28 (02) :355-+
[2]   ENDOPROTEASE IN PLASMODIUM-YOELII-NIGERIENSIS [J].
AISSI, E ;
CHARET, P ;
BOUQUELET, S ;
BIGUET, J .
COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY B-BIOCHEMISTRY & MOLECULAR BIOLOGY, 1983, 74 (03) :559-566
[3]  
AZUMA T, 1989, J BIOL CHEM, V264, P16748
[4]   HEMOGLOBIN - STRUCTURAL-CHANGES RELATED TO LIGAND-BINDING AND ITS ALLOSTERIC MECHANISM [J].
BALDWIN, J ;
CHOTHIA, C .
JOURNAL OF MOLECULAR BIOLOGY, 1979, 129 (02) :175-+
[5]  
BALL EG, 1948, J BIOL CHEM, V175, P547
[6]  
Beavis R C, 1989, Rapid Commun Mass Spectrom, V3, P436, DOI 10.1002/rcm.1290031208
[7]  
Beavis R C, 1989, Rapid Commun Mass Spectrom, V3, P432, DOI 10.1002/rcm.1290031207
[8]   HIGH-ACCURACY MOLECULAR MASS DETERMINATION OF PROTEINS USING MATRIX-ASSISTED LASER DESORPTION MASS-SPECTROMETRY [J].
BEAVIS, RC ;
CHAIT, BT .
ANALYTICAL CHEMISTRY, 1990, 62 (17) :1836-1840
[9]   RAPID, SENSITIVE ANALYSIS OF PROTEIN MIXTURES BY MASS-SPECTROMETRY [J].
BEAVIS, RC ;
CHAIT, BT .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1990, 87 (17) :6873-6877
[10]  
BEYCHOK S, 1967, J BIOL CHEM, V242, P2460