5bwy - Revision history

OCA at 11:17, 10 January 2024

OCA — Wed, 10 Jan 2024 11:17:24 GMT

←Older revision		Revision as of 11:17, 10 January 2024
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[5bwy]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Plasmodium_falciparum Plasmodium falciparum]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5BWY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5BWY FirstGlance]. <br>		<table><tr><td colspan='2'>[[5bwy]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Plasmodium_falciparum Plasmodium falciparum]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5BWY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5BWY FirstGlance]. <br>
-	</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5bwy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5bwy OCA], [https://pdbe.org/5bwy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5bwy RCSB], [https://www.ebi.ac.uk/pdbsum/5bwy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5bwy ProSAT]</span></td></tr>	+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution\|Resolution]] 2.644Å</td></tr>
		+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5bwy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5bwy OCA], [https://pdbe.org/5bwy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5bwy RCSB], [https://www.ebi.ac.uk/pdbsum/5bwy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5bwy ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==

OCA at 06:11, 7 June 2023

OCA — Wed, 07 Jun 2023 06:11:31 GMT

←Older revision		Revision as of 06:11, 7 June 2023
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	==Structure of proplasmepsin II from Plasmodium falciparum, Space Group P43212==		==Structure of proplasmepsin II from Plasmodium falciparum, Space Group P43212==
-	<StructureSection load='5bwy' size='340' side='right' caption='[[5bwy]], [[Resolution\|resolution]] 2.64Å' scene=''>	+	<StructureSection load='5bwy' size='340' side='right'caption='[[5bwy]], [[Resolution\|resolution]] 2.64Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5bwy]] is a 1 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~Plafa Plafa~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5BWY OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5BWY FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5bwy]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Plasmodium_falciparum Plasmodium falciparum]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5BWY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5BWY FirstGlance]. <br>
-	</td></tr>~~<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PFAG_05140 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=5833 PLAFA])</td></tr>~~	+	</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5bwy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5bwy OCA], [https://pdbe.org/5bwy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5bwy RCSB], [https://www.ebi.ac.uk/pdbsum/5bwy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5bwy ProSAT]</span></td></tr>
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5bwy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5bwy OCA], [~~http~~://pdbe.org/5bwy PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5bwy RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5bwy PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5bwy ProSAT]</span></td></tr>	+
	</table>		</table>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/PLM2_PLAFX PLM2_PLAFX] During the asexual blood stage, participates in initial cleavage of native host hemoglobin (Hb) resulting in Hb denaturation (PubMed:8844673, PubMed:11782538, PubMed:15574427). May cleave preferentially denatured hemoglobin that has been cleaved by PMI (PubMed:8844673). Digestion of host Hb is an essential step which provides the parasite with amino acids for protein synthesis, and regulates osmolarity (Probable).<ref>PMID:11782538</ref> <ref>PMID:15574427</ref> <ref>PMID:8844673</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Plafa~~]]	+	[[Category: Large Structures]]
-	[[Category: Akopjana, I]]	+	[[Category: Plasmodium falciparum]]
-	[[Category: Jaudzems, K]]	+	[[Category: Akopjana I]]
-	[[Category: Recacha, R]]	+	[[Category: Jaudzems K]]
-	[[Category: Tars, K]]	+	[[Category: Recacha R]]
-	~~[[Category: Hydrolase]]~~	+	[[Category: Tars K]]
-	~~[[Category: Malaria~~]]	+

OCA at 06:17, 18 April 2018

OCA — Wed, 18 Apr 2018 06:17:50 GMT

←Older revision		Revision as of 06:17, 18 April 2018
Line 9:		Line 9:
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
-	~~The malarial aspartic proteinases (plasmepsins) have been discovered in several species of~~ Plasmodium~~, including all four of the human malarial pathogens. In P.~~falciparum~~, plasmepsins I, II,~~ IV ~~and HAP have been directly implicated in hemoglobin degradation during malaria infection, and are now considered targets~~ for ~~anti-malarial drug design~~. ~~The plasmepsins are produced from inactive zymogens~~, ~~proplasmepsins, having unusually long N-terminal prosegments of more than 120 amino acids. Structural and biochemical evidence suggests that~~ the ~~conversion process~~ of ~~proplasmepsins to plasmepsins differs substantially from~~ the ~~gastric and plant aspartic proteinases. Instead~~ of ~~blocking substrate access to a pre-formed active site~~, the prosegment ~~enforces a conformation in which proplasmepsin cannot form a functional active site. We have~~ determined ~~crystal structures of plasmepsin and proplasmepsin from P~~.~~vivax~~. ~~The three-dimensional structure of P.vivax plasmepsin is typical of~~ the ~~monomeric aspartic proteinases~~, ~~and the structure of~~ P.vivax ~~proplasmepsin is similar~~ to ~~that of~~ P.falciparum ~~proplasmepsin II~~. ~~A dramatic refolding of the mature N terminus~~ and ~~a large (18 degrees ) reorientation~~ of the ~~N-domain between P.vivax~~ proplasmepsin ~~and plasmepsin results in a severe distortion of the active site region of the zymogen relative to that of the mature enzyme. The present~~ structures ~~confirm that~~ the ~~mode of inactivation observed originally~~ in ~~P.falciparum proplasmepsin II, i.e. an incompletely formed active site, is a true structural feature and likely represents~~ the ~~general mode of~~ inactivation of the ~~related proplasmepsins~~.	+	Plasmepsin IV from Plasmodium falciparum (PM IV) is a promising target for the development of novel antimalarial drugs. Here, the crystal structure of the truncated zymogen of PM IV (pPM IV), consisting of the mature enzyme plus a prosegment of 47 residues, has been determined at 1.5 A resolution. pPM IV presents the fold previously described for studied proplasmepsins, displaying closer similarities to proplasmepin IV from P. vivax (pPvPM) than to the other two proplasmepsins from P. falciparum. The study and comparison of the pPM IV structure with the proplasmepsin structures described previously provide information about the similarities and differences in the inactivation-activation mechanisms among the plasmepsin zymogens.

-	~~Structural insights into~~ the ~~activation~~ of ~~P. vivax plasmepsin~~.,~~Bernstein NK~~, ~~Cherney MM~~, ~~Yowell CA~~, ~~Dame JB~~, ~~James MN J Mol~~ Biol. ~~2003 Jun 6~~;~~329~~(3):~~505~~-24. PMID:~~12767832~~<ref>PMID:~~12767832~~</ref>	+	Crystal structure of Plasmodium falciparum proplasmepsin IV: the plasticity of proplasmepsins.,Recacha R, Jaudzems K, Akopjana I, Jirgensons A, Tars K Acta Crystallogr F Struct Biol Commun. 2016 Sep;72(Pt 9):659-66. doi:, 10.1107/S2053230X16011663. Epub 2016 Aug 9. PMID:27599854<ref>PMID:27599854</ref>

	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	</div>		</div>
	<div class="pdbe-citations 5bwy" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5bwy" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Plasmepsin\|Plasmepsin]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 08:02, 17 January 2018

OCA — Wed, 17 Jan 2018 08:02:38 GMT

←Older revision		Revision as of 08:02, 17 January 2018
Line 1:		Line 1:
		+
	==Structure of proplasmepsin II from Plasmodium falciparum, Space Group P43212==		==Structure of proplasmepsin II from Plasmodium falciparum, Space Group P43212==
	<StructureSection load='5bwy' size='340' side='right' caption='[[5bwy]], [[Resolution\|resolution]] 2.64Å' scene=''>		<StructureSection load='5bwy' size='340' side='right' caption='[[5bwy]], [[Resolution\|resolution]] 2.64Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5bwy]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5BWY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5BWY FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5bwy]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Plafa Plafa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5BWY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5BWY FirstGlance]. <br>
-	</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5bwy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5bwy OCA], [http://pdbe.org/5bwy PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5bwy RCSB], [http://www.ebi.ac.uk/pdbsum/5bwy PDBsum]</span></td></tr>	+	</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PFAG_05140 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=5833 PLAFA])</td></tr>
		+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5bwy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5bwy OCA], [http://pdbe.org/5bwy PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5bwy RCSB], [http://www.ebi.ac.uk/pdbsum/5bwy PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5bwy ProSAT]</span></td></tr>
	</table>		</table>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
-	~~Proplasmepsin II is the zymogen~~ of ~~plasmepsin~~ II, ~~an aspartic proteinase used by Plasmodiumfalciparum to digest~~ hemoglobin during ~~the blood stage of~~ malaria. ~~A large shift between the~~ N-~~domain~~ and the ~~central and C-domains~~ of ~~proplasmepsin II opens~~ the active site ~~cleft~~, ~~preventing~~ the ~~formation of~~ a functional ~~aspartic proteinase~~ active site. ~~This mode~~ of ~~inhibition~~ of ~~catalytic activity has not been observed in any other aspartic proteinase zymogen~~. ~~Instead~~ of ~~occluding a pre-formed active site, as in~~ the ~~gastric~~ aspartic ~~proteinase zymogens~~, the ~~prosegment~~ of proplasmepsin II ~~interacts extensively with~~ the C-domain and ~~serves as~~ a ~~'harness'~~ to ~~keep~~ the ~~domains apart~~. ~~Disruption~~ of ~~key salt bridges at low pH may be important~~ in ~~activation~~.	+	The malarial aspartic proteinases (plasmepsins) have been discovered in several species of Plasmodium, including all four of the human malarial pathogens. In P.falciparum, plasmepsins I, II, IV and HAP have been directly implicated in hemoglobin degradation during malaria infection, and are now considered targets for anti-malarial drug design. The plasmepsins are produced from inactive zymogens, proplasmepsins, having unusually long N-terminal prosegments of more than 120 amino acids. Structural and biochemical evidence suggests that the conversion process of proplasmepsins to plasmepsins differs substantially from the gastric and plant aspartic proteinases. Instead of blocking substrate access to a pre-formed active site, the prosegment enforces a conformation in which proplasmepsin cannot form a functional active site. We have determined crystal structures of plasmepsin and proplasmepsin from P.vivax. The three-dimensional structure of P.vivax plasmepsin is typical of the monomeric aspartic proteinases, and the structure of P.vivax proplasmepsin is similar to that of P.falciparum proplasmepsin II. A dramatic refolding of the mature N terminus and a large (18 degrees ) reorientation of the N-domain between P.vivax proplasmepsin and plasmepsin results in a severe distortion of the active site region of the zymogen relative to that of the mature enzyme. The present structures confirm that the mode of inactivation observed originally in P.falciparum proplasmepsin II, i.e. an incompletely formed active site, is a true structural feature and likely represents the general mode of inactivation of the related proplasmepsins.

-	~~Crystal structure of~~ the ~~novel aspartic proteinase zymogen proplasmepsin II from plasmodium falciparum~~.,Bernstein NK, Cherney MM, ~~Loetscher H~~, ~~Ridley RG~~, James MN ~~Nat Struct~~ Biol. ~~1999 Jan;~~6(1):32-7. PMID:~~9886289~~<ref>PMID:~~9886289~~</ref>	+	Structural insights into the activation of P. vivax plasmepsin.,Bernstein NK, Cherney MM, Yowell CA, Dame JB, James MN J Mol Biol. 2003 Jun 6;329(3):505-24. PMID:12767832<ref>PMID:12767832</ref>

	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
Line 18:		Line 20:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Plafa]]
	[[Category: Akopjana, I]]		[[Category: Akopjana, I]]
	[[Category: Jaudzems, K]]		[[Category: Jaudzems, K]]

OCA at 13:51, 16 December 2015

OCA — Wed, 16 Dec 2015 13:51:50 GMT

←Older revision		Revision as of 13:51, 16 December 2015
Line 1:		Line 1:
-	'''~~Unreleased~~ structure'''	+	==Structure of proplasmepsin II from Plasmodium falciparum, Space Group P43212==
		+	<StructureSection load='5bwy' size='340' side='right' caption='[[5bwy]], [[Resolution\|resolution]] 2.64Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[5bwy]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5BWY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5BWY FirstGlance]. <br>
		+	</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5bwy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5bwy OCA], [http://pdbe.org/5bwy PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5bwy RCSB], [http://www.ebi.ac.uk/pdbsum/5bwy PDBsum]</span></td></tr>
		+	</table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Proplasmepsin II is the zymogen of plasmepsin II, an aspartic proteinase used by Plasmodiumfalciparum to digest hemoglobin during the blood stage of malaria. A large shift between the N-domain and the central and C-domains of proplasmepsin II opens the active site cleft, preventing the formation of a functional aspartic proteinase active site. This mode of inhibition of catalytic activity has not been observed in any other aspartic proteinase zymogen. Instead of occluding a pre-formed active site, as in the gastric aspartic proteinase zymogens, the prosegment of proplasmepsin II interacts extensively with the C-domain and serves as a 'harness' to keep the domains apart. Disruption of key salt bridges at low pH may be important in activation.

-	~~The entry 5bwy is ON HOLD until Paper Publication~~	+	Crystal structure of the novel aspartic proteinase zymogen proplasmepsin II from plasmodium falciparum.,Bernstein NK, Cherney MM, Loetscher H, Ridley RG, James MN Nat Struct Biol. 1999 Jan;6(1):32-7. PMID:9886289<ref>PMID:9886289</ref>

-	~~Authors: Recacha~~, R.~~, Akopjana, I~~.~~, Tars, K., Jaudzems, K~~.	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-		+	</div>
-	~~Description~~: ~~Structure of proplasmepsin II from Plasmodium falciparum, Space Group P43212~~	+	<div class="pdbe-citations 5bwy" style="background-color:#fffaf0;"></div>
-	[[Category: ~~Unreleased Structures~~]]	+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Akopjana, I]]
	[[Category: Jaudzems, K]]		[[Category: Jaudzems, K]]
		+	[[Category: Recacha, R]]
	[[Category: Tars, K]]		[[Category: Tars, K]]
-	[[Category: ~~Akopjana, I~~]]	+	[[Category: Hydrolase]]
-	[[Category: ~~Recacha, R~~]]	+	[[Category: Malaria]]

OCA at 11:58, 15 July 2015

OCA — Wed, 15 Jul 2015 11:58:42 GMT

←Older revision		Revision as of 11:58, 15 July 2015
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 5bwy is ON HOLD	+	The entry 5bwy is ON HOLD until Paper Publication

	Authors: Recacha, R., Akopjana, I., Tars, K., Jaudzems, K.		Authors: Recacha, R., Akopjana, I., Tars, K., Jaudzems, K.

OCA: Protected "5bwy" [edit=sysop:move=sysop]

OCA — Wed, 17 Jun 2015 14:00:27 GMT

Protected "5bwy" [edit=sysop:move=sysop]

←Older revision

Revision as of 14:00, 17 June 2015

OCA: New page: '''Unreleased structure''' The entry 5bwy is ON HOLD Authors: Recacha, R., Akopjana, I., Tars, K., Jaudzems, K. Description: Structure of proplasmepsin II from Plasmodium falciparum, S...

OCA — Wed, 17 Jun 2015 14:00:25 GMT

New page: '''Unreleased structure''' The entry 5bwy is ON HOLD Authors: Recacha, R., Akopjana, I., Tars, K., Jaudzems, K. Description: Structure of proplasmepsin II from Plasmodium falciparum, S...

New page

'''Unreleased structure'''

The entry 5bwy is ON HOLD

Authors: Recacha, R., Akopjana, I., Tars, K., Jaudzems, K.

Description: Structure of proplasmepsin II from Plasmodium falciparum, Space Group P43212
[[Category: Unreleased Structures]]
[[Category: Jaudzems, K]]
[[Category: Tars, K]]
[[Category: Akopjana, I]]
[[Category: Recacha, R]]