Loading…
Biosynthesis and Maturation of the Malaria Aspartic Hemoglobinases Plasmepsins I and II
During the intraerythrocytic stage of infection, the malaria parasite Plasmodium falciparum digests most of the host cell hemoglobin. Hemoglobin degradation occurs in the acidic digestive vacuole and is essential for the survival of the parasite. Two aspartic proteases, plasmepsins I and II, have be...
Saved in:
Published in: | The Journal of biological chemistry 1997-06, Vol.272 (23), p.14961-14968 |
---|---|
Main Authors: | , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
cited_by | cdi_FETCH-LOGICAL-c431t-634c5be81b62fb0f6c6dec89708c84b0c1c06960bc53783fb55bc37e3291e8ab3 |
---|---|
cites | cdi_FETCH-LOGICAL-c431t-634c5be81b62fb0f6c6dec89708c84b0c1c06960bc53783fb55bc37e3291e8ab3 |
container_end_page | 14968 |
container_issue | 23 |
container_start_page | 14961 |
container_title | The Journal of biological chemistry |
container_volume | 272 |
creator | Francis, S E Banerjee, R Goldberg, D E |
description | During the intraerythrocytic stage of infection, the malaria parasite Plasmodium falciparum digests most of the host cell hemoglobin. Hemoglobin degradation occurs in the acidic digestive vacuole and is essential
for the survival of the parasite. Two aspartic proteases, plasmepsins I and II, have been isolated from the vacuole and shown
to make the initial cleavages in the hemoglobin molecule. We have studied the biosynthesis of these two enzymes. Plasmepsin
I is synthesized and processed to the mature form soon after the parasite invades the red blood cell, while plasmepsin II
synthesis is delayed until later in development. Otherwise, biosynthesis of the plasmepsins is identical. The proplasmepsins
are type II integral membrane proteins that are transported through the secretory pathway before cleavage to the soluble form.
They are not glycosylated in vivo , despite the presence of several potential glycosylation sites. Proplasmepsin maturation appears to require acidic conditions
and is reversibly inhibited by the tripeptide aldehydes N-acetyl - l - leucyl - l - leucyl -norleucinal and N-acetyl - l - leucyl - l - leucyl -methional. These compounds are known to inhibit cysteine proteases and the chymotryptic activity of proteasomes but not aspartic
proteases. However, proplasmepsin processing is not blocked by other cysteine protease inhibitors, nor by the proteasome inhibitor
lactacystin. Processing is also not blocked by aspartic protease inhibitors. This inhibitor profile suggests that unlike most
other aspartic proteases, proplasmepsin maturation may not be autocatalytic in vivo , but instead could require the action of an unusual processing enzyme. Compounds that block processing are expected to be
potent antimalarials. |
doi_str_mv | 10.1074/jbc.272.23.14961 |
format | article |
fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_79045556</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>79045556</sourcerecordid><originalsourceid>FETCH-LOGICAL-c431t-634c5be81b62fb0f6c6dec89708c84b0c1c06960bc53783fb55bc37e3291e8ab3</originalsourceid><addsrcrecordid>eNpVkMFLwzAUh4Moc07vXoQexFtr0jRpc5xD3UDRg6K3kGTpmtE2M69F9t9btyH4Lg_e7_e-w4fQJcEJwXl2u9YmSfM0SWlCMsHJERoTXNCYMvJ5jMYYpyQWKStO0RnAGg-TCTJCI0G4yLgYo48752HbdpUFB5Fql9Gz6vqgOufbyJfREAyXWgWnoilsVOiciea28avaa9cqsBC91goauwHXQrTYMRaLc3RSqhrsxWFP0PvD_dtsHj-9PC5m06fYZJR0MaeZYdoWRPO01Ljkhi-tKUSOC1NkGhtiMBcca8NoXtBSM6YNzS1NBbGF0nSCbvbcTfBfvYVONg6MrWvVWt-DzAXOGGN8KOJ90QQPEGwpN8E1KmwlwfLXpRxcysGlTKncuRxerg7sXjd2-fdwkDfk1_u8cqvq2wUrtfOmss1_zA8BX3vZ</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>79045556</pqid></control><display><type>article</type><title>Biosynthesis and Maturation of the Malaria Aspartic Hemoglobinases Plasmepsins I and II</title><source>ScienceDirect</source><creator>Francis, S E ; Banerjee, R ; Goldberg, D E</creator><creatorcontrib>Francis, S E ; Banerjee, R ; Goldberg, D E</creatorcontrib><description>During the intraerythrocytic stage of infection, the malaria parasite Plasmodium falciparum digests most of the host cell hemoglobin. Hemoglobin degradation occurs in the acidic digestive vacuole and is essential
for the survival of the parasite. Two aspartic proteases, plasmepsins I and II, have been isolated from the vacuole and shown
to make the initial cleavages in the hemoglobin molecule. We have studied the biosynthesis of these two enzymes. Plasmepsin
I is synthesized and processed to the mature form soon after the parasite invades the red blood cell, while plasmepsin II
synthesis is delayed until later in development. Otherwise, biosynthesis of the plasmepsins is identical. The proplasmepsins
are type II integral membrane proteins that are transported through the secretory pathway before cleavage to the soluble form.
They are not glycosylated in vivo , despite the presence of several potential glycosylation sites. Proplasmepsin maturation appears to require acidic conditions
and is reversibly inhibited by the tripeptide aldehydes N-acetyl - l - leucyl - l - leucyl -norleucinal and N-acetyl - l - leucyl - l - leucyl -methional. These compounds are known to inhibit cysteine proteases and the chymotryptic activity of proteasomes but not aspartic
proteases. However, proplasmepsin processing is not blocked by other cysteine protease inhibitors, nor by the proteasome inhibitor
lactacystin. Processing is also not blocked by aspartic protease inhibitors. This inhibitor profile suggests that unlike most
other aspartic proteases, proplasmepsin maturation may not be autocatalytic in vivo , but instead could require the action of an unusual processing enzyme. Compounds that block processing are expected to be
potent antimalarials.</description><identifier>ISSN: 0021-9258</identifier><identifier>EISSN: 1083-351X</identifier><identifier>DOI: 10.1074/jbc.272.23.14961</identifier><identifier>PMID: 9169469</identifier><language>eng</language><publisher>United States: American Society for Biochemistry and Molecular Biology</publisher><subject>Amino Acid Sequence ; Animals ; Antibodies ; Aspartic Acid Endopeptidases - biosynthesis ; Aspartic Acid Endopeptidases - metabolism ; Erythrocytes - parasitology ; Hemoglobins - metabolism ; Humans ; Immunoblotting ; Membrane Proteins - biosynthesis ; Membrane Proteins - metabolism ; Molecular Sequence Data ; Oligopeptides - pharmacology ; Peptide Fragments - chemistry ; Peptide Fragments - immunology ; Plasmodium falciparum - enzymology ; Plasmodium falciparum - pathogenicity ; Protease Inhibitors - pharmacology ; Protein Biosynthesis ; Protozoan Proteins ; Recombinant Proteins - biosynthesis ; Recombinant Proteins - metabolism ; Vacuoles - enzymology</subject><ispartof>The Journal of biological chemistry, 1997-06, Vol.272 (23), p.14961-14968</ispartof><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c431t-634c5be81b62fb0f6c6dec89708c84b0c1c06960bc53783fb55bc37e3291e8ab3</citedby><cites>FETCH-LOGICAL-c431t-634c5be81b62fb0f6c6dec89708c84b0c1c06960bc53783fb55bc37e3291e8ab3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,778,782,27911,27912</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/9169469$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Francis, S E</creatorcontrib><creatorcontrib>Banerjee, R</creatorcontrib><creatorcontrib>Goldberg, D E</creatorcontrib><title>Biosynthesis and Maturation of the Malaria Aspartic Hemoglobinases Plasmepsins I and II</title><title>The Journal of biological chemistry</title><addtitle>J Biol Chem</addtitle><description>During the intraerythrocytic stage of infection, the malaria parasite Plasmodium falciparum digests most of the host cell hemoglobin. Hemoglobin degradation occurs in the acidic digestive vacuole and is essential
for the survival of the parasite. Two aspartic proteases, plasmepsins I and II, have been isolated from the vacuole and shown
to make the initial cleavages in the hemoglobin molecule. We have studied the biosynthesis of these two enzymes. Plasmepsin
I is synthesized and processed to the mature form soon after the parasite invades the red blood cell, while plasmepsin II
synthesis is delayed until later in development. Otherwise, biosynthesis of the plasmepsins is identical. The proplasmepsins
are type II integral membrane proteins that are transported through the secretory pathway before cleavage to the soluble form.
They are not glycosylated in vivo , despite the presence of several potential glycosylation sites. Proplasmepsin maturation appears to require acidic conditions
and is reversibly inhibited by the tripeptide aldehydes N-acetyl - l - leucyl - l - leucyl -norleucinal and N-acetyl - l - leucyl - l - leucyl -methional. These compounds are known to inhibit cysteine proteases and the chymotryptic activity of proteasomes but not aspartic
proteases. However, proplasmepsin processing is not blocked by other cysteine protease inhibitors, nor by the proteasome inhibitor
lactacystin. Processing is also not blocked by aspartic protease inhibitors. This inhibitor profile suggests that unlike most
other aspartic proteases, proplasmepsin maturation may not be autocatalytic in vivo , but instead could require the action of an unusual processing enzyme. Compounds that block processing are expected to be
potent antimalarials.</description><subject>Amino Acid Sequence</subject><subject>Animals</subject><subject>Antibodies</subject><subject>Aspartic Acid Endopeptidases - biosynthesis</subject><subject>Aspartic Acid Endopeptidases - metabolism</subject><subject>Erythrocytes - parasitology</subject><subject>Hemoglobins - metabolism</subject><subject>Humans</subject><subject>Immunoblotting</subject><subject>Membrane Proteins - biosynthesis</subject><subject>Membrane Proteins - metabolism</subject><subject>Molecular Sequence Data</subject><subject>Oligopeptides - pharmacology</subject><subject>Peptide Fragments - chemistry</subject><subject>Peptide Fragments - immunology</subject><subject>Plasmodium falciparum - enzymology</subject><subject>Plasmodium falciparum - pathogenicity</subject><subject>Protease Inhibitors - pharmacology</subject><subject>Protein Biosynthesis</subject><subject>Protozoan Proteins</subject><subject>Recombinant Proteins - biosynthesis</subject><subject>Recombinant Proteins - metabolism</subject><subject>Vacuoles - enzymology</subject><issn>0021-9258</issn><issn>1083-351X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1997</creationdate><recordtype>article</recordtype><recordid>eNpVkMFLwzAUh4Moc07vXoQexFtr0jRpc5xD3UDRg6K3kGTpmtE2M69F9t9btyH4Lg_e7_e-w4fQJcEJwXl2u9YmSfM0SWlCMsHJERoTXNCYMvJ5jMYYpyQWKStO0RnAGg-TCTJCI0G4yLgYo48752HbdpUFB5Fql9Gz6vqgOufbyJfREAyXWgWnoilsVOiciea28avaa9cqsBC91goauwHXQrTYMRaLc3RSqhrsxWFP0PvD_dtsHj-9PC5m06fYZJR0MaeZYdoWRPO01Ljkhi-tKUSOC1NkGhtiMBcca8NoXtBSM6YNzS1NBbGF0nSCbvbcTfBfvYVONg6MrWvVWt-DzAXOGGN8KOJ90QQPEGwpN8E1KmwlwfLXpRxcysGlTKncuRxerg7sXjd2-fdwkDfk1_u8cqvq2wUrtfOmss1_zA8BX3vZ</recordid><startdate>19970606</startdate><enddate>19970606</enddate><creator>Francis, S E</creator><creator>Banerjee, R</creator><creator>Goldberg, D E</creator><general>American Society for Biochemistry and Molecular Biology</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>19970606</creationdate><title>Biosynthesis and Maturation of the Malaria Aspartic Hemoglobinases Plasmepsins I and II</title><author>Francis, S E ; Banerjee, R ; Goldberg, D E</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c431t-634c5be81b62fb0f6c6dec89708c84b0c1c06960bc53783fb55bc37e3291e8ab3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1997</creationdate><topic>Amino Acid Sequence</topic><topic>Animals</topic><topic>Antibodies</topic><topic>Aspartic Acid Endopeptidases - biosynthesis</topic><topic>Aspartic Acid Endopeptidases - metabolism</topic><topic>Erythrocytes - parasitology</topic><topic>Hemoglobins - metabolism</topic><topic>Humans</topic><topic>Immunoblotting</topic><topic>Membrane Proteins - biosynthesis</topic><topic>Membrane Proteins - metabolism</topic><topic>Molecular Sequence Data</topic><topic>Oligopeptides - pharmacology</topic><topic>Peptide Fragments - chemistry</topic><topic>Peptide Fragments - immunology</topic><topic>Plasmodium falciparum - enzymology</topic><topic>Plasmodium falciparum - pathogenicity</topic><topic>Protease Inhibitors - pharmacology</topic><topic>Protein Biosynthesis</topic><topic>Protozoan Proteins</topic><topic>Recombinant Proteins - biosynthesis</topic><topic>Recombinant Proteins - metabolism</topic><topic>Vacuoles - enzymology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Francis, S E</creatorcontrib><creatorcontrib>Banerjee, R</creatorcontrib><creatorcontrib>Goldberg, D E</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>The Journal of biological chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Francis, S E</au><au>Banerjee, R</au><au>Goldberg, D E</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Biosynthesis and Maturation of the Malaria Aspartic Hemoglobinases Plasmepsins I and II</atitle><jtitle>The Journal of biological chemistry</jtitle><addtitle>J Biol Chem</addtitle><date>1997-06-06</date><risdate>1997</risdate><volume>272</volume><issue>23</issue><spage>14961</spage><epage>14968</epage><pages>14961-14968</pages><issn>0021-9258</issn><eissn>1083-351X</eissn><abstract>During the intraerythrocytic stage of infection, the malaria parasite Plasmodium falciparum digests most of the host cell hemoglobin. Hemoglobin degradation occurs in the acidic digestive vacuole and is essential
for the survival of the parasite. Two aspartic proteases, plasmepsins I and II, have been isolated from the vacuole and shown
to make the initial cleavages in the hemoglobin molecule. We have studied the biosynthesis of these two enzymes. Plasmepsin
I is synthesized and processed to the mature form soon after the parasite invades the red blood cell, while plasmepsin II
synthesis is delayed until later in development. Otherwise, biosynthesis of the plasmepsins is identical. The proplasmepsins
are type II integral membrane proteins that are transported through the secretory pathway before cleavage to the soluble form.
They are not glycosylated in vivo , despite the presence of several potential glycosylation sites. Proplasmepsin maturation appears to require acidic conditions
and is reversibly inhibited by the tripeptide aldehydes N-acetyl - l - leucyl - l - leucyl -norleucinal and N-acetyl - l - leucyl - l - leucyl -methional. These compounds are known to inhibit cysteine proteases and the chymotryptic activity of proteasomes but not aspartic
proteases. However, proplasmepsin processing is not blocked by other cysteine protease inhibitors, nor by the proteasome inhibitor
lactacystin. Processing is also not blocked by aspartic protease inhibitors. This inhibitor profile suggests that unlike most
other aspartic proteases, proplasmepsin maturation may not be autocatalytic in vivo , but instead could require the action of an unusual processing enzyme. Compounds that block processing are expected to be
potent antimalarials.</abstract><cop>United States</cop><pub>American Society for Biochemistry and Molecular Biology</pub><pmid>9169469</pmid><doi>10.1074/jbc.272.23.14961</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
fulltext | fulltext |
identifier | ISSN: 0021-9258 |
ispartof | The Journal of biological chemistry, 1997-06, Vol.272 (23), p.14961-14968 |
issn | 0021-9258 1083-351X |
language | eng |
recordid | cdi_proquest_miscellaneous_79045556 |
source | ScienceDirect |
subjects | Amino Acid Sequence Animals Antibodies Aspartic Acid Endopeptidases - biosynthesis Aspartic Acid Endopeptidases - metabolism Erythrocytes - parasitology Hemoglobins - metabolism Humans Immunoblotting Membrane Proteins - biosynthesis Membrane Proteins - metabolism Molecular Sequence Data Oligopeptides - pharmacology Peptide Fragments - chemistry Peptide Fragments - immunology Plasmodium falciparum - enzymology Plasmodium falciparum - pathogenicity Protease Inhibitors - pharmacology Protein Biosynthesis Protozoan Proteins Recombinant Proteins - biosynthesis Recombinant Proteins - metabolism Vacuoles - enzymology |
title | Biosynthesis and Maturation of the Malaria Aspartic Hemoglobinases Plasmepsins I and II |
url | http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-15T17%3A11%3A59IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Biosynthesis%20and%20Maturation%20of%20the%20Malaria%20Aspartic%20Hemoglobinases%20Plasmepsins%20I%20and%20II&rft.jtitle=The%20Journal%20of%20biological%20chemistry&rft.au=Francis,%20S%20E&rft.date=1997-06-06&rft.volume=272&rft.issue=23&rft.spage=14961&rft.epage=14968&rft.pages=14961-14968&rft.issn=0021-9258&rft.eissn=1083-351X&rft_id=info:doi/10.1074/jbc.272.23.14961&rft_dat=%3Cproquest_cross%3E79045556%3C/proquest_cross%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c431t-634c5be81b62fb0f6c6dec89708c84b0c1c06960bc53783fb55bc37e3291e8ab3%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=79045556&rft_id=info:pmid/9169469&rfr_iscdi=true |