6x44: Difference between revisions

Latest revision as of 14:41, 18 October 2023

High Resolution Crystal Structure Analysis of SERA5 proenzyme from plasmodium falciparum

Structural highlights

6x44 is a 2 chain structure with sequence from Plasmodium falciparum. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.1973395Å
Ligands:	PEG
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

SERA5_PLAF7 Plays an essential role during the asexual blood stage development by controlling the kinetics of merozoite egress from host erythrocytes (PubMed:25599609, PubMed:28683142). Specifically, prevents premature rupture of the parasitophorous vacuole and host erythrocyte membranes (PubMed:28683142).^[1] ^[2] May prevent merozoite phagocytosis by host monocytes via interaction with host VTN at the merozoite surface (By similarity). Plays a role in parasite growth (By similarity).[UniProtKB:P69193] Protease activity is controversial (PubMed:25599609). Has been shown in a number of studies to have protease activity towards a synthetic peptide in vitro (PubMed:13679369, PubMed:24769454, PubMed:29716996). Has also been shown to lack protease activity towards a synthetic peptide in vitro (PubMed:25599609).^[3] ^[4] ^[5] ^[6]

Publication Abstract from PubMed

PfSERA5, a significantly abundant protein present within the parasitophorous vacuole (PV) and essential for normal growth during the blood-stage life cycle of the malaria parasite Plasmodium falciparum, displays structural similarity to many other cysteine proteases. However, PfSERA5 does not exhibit any detectable protease activity and therefore the role of the PfSERA5 papain-like domain (PfSERA5E), thought to remain bound to its cognate prodomain, remains unknown. In this study, we present a revised structure of the central PfSERA5E domain at a resolution of 1.2 A, and the first structure of the "zymogen" of this papain-like domain including its cognate prodomain (PfSERA5PE) to 2.2 A resolution. PfSERA5PE is somewhat structurally similar to that of other known proenzymes, retaining the conserved overall folding and orientation of the prodomain through, and occluding, the archetypal papain-like catalytic triad "active-site" cleft, in the same reverse direction as conventional prodomains. Our findings are congruent with previously identified structures of PfSERA5E and of similar "zymogens" and provide a foundation for further investigation into the function of PfSERA5.

Structure of the Plasmodium falciparum PfSERA5 pseudo-zymogen.,Smith NA, Clarke OB, Lee M, Hodder AN, Smith BJ Protein Sci. 2020 Sep 21. doi: 10.1002/pro.3956. PMID:32955133^[7]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Stallmach R, Kavishwar M, Withers-Martinez C, Hackett F, Collins CR, Howell SA, Yeoh S, Knuepfer E, Atid AJ, Holder AA, Blackman MJ. Plasmodium falciparum SERA5 plays a non-enzymatic role in the malarial asexual blood-stage lifecycle. Mol Microbiol. 2015 Apr;96(2):368-87. PMID:25599609 doi:10.1111/mmi.12941
↑ Collins CR, Hackett F, Atid J, Tan MSY, Blackman MJ. The Plasmodium falciparum pseudoprotease SERA5 regulates the kinetics and efficiency of malaria parasite egress from host erythrocytes. PLoS Pathog. 2017 Jul 6;13(7):e1006453. PMID:28683142 doi:10.1371/journal.ppat.1006453
↑ Hodder AN, Drew DR, Epa VC, Delorenzi M, Bourgon R, Miller SK, Moritz RL, Frecklington DF, Simpson RJ, Speed TP, Pike RN, Crabb BS. Enzymic, phylogenetic, and structural characterization of the unusual papain-like protease domain of Plasmodium falciparum SERA5. J Biol Chem. 2003 Nov 28;278(48):48169-77. PMID:13679369 doi:10.1074/jbc.M306755200
↑ Kanodia S, Kumar G, Rizzi L, Pedretti A, Hodder AN, Romeo S, Malhotra P. Synthetic peptides derived from the C-terminal 6kDa region of Plasmodium falciparum SERA5 inhibit the enzyme activity and malaria parasite development. Biochim Biophys Acta. 2014 Sep;1840(9):2765-75. PMID:24769454 doi:10.1016/j.bbagen.2014.04.013
↑ Stallmach R, Kavishwar M, Withers-Martinez C, Hackett F, Collins CR, Howell SA, Yeoh S, Knuepfer E, Atid AJ, Holder AA, Blackman MJ. Plasmodium falciparum SERA5 plays a non-enzymatic role in the malarial asexual blood-stage lifecycle. Mol Microbiol. 2015 Apr;96(2):368-87. PMID:25599609 doi:10.1111/mmi.12941
↑ Iyer GR, Singh S, Kaur I, Agarwal S, Siddiqui MA, Bansal A, Kumar G, Saini E, Paul G, Mohmmed A, Chitnis CE, Malhotra P. Calcium-dependent phosphorylation of Plasmodium falciparum serine repeat antigen 5 triggers merozoite egress. J Biol Chem. 2018 Jun 22;293(25):9736-9746. PMID:29716996 doi:10.1074/jbc.RA117.001540
↑ Smith NA, Clarke OB, Lee M, Hodder AN, Smith BJ. Structure of the Plasmodium falciparum PfSERA5 pseudo-zymogen. Protein Sci. 2020 Sep 21. doi: 10.1002/pro.3956. PMID:32955133 doi:https://dx.doi.org/10.1002/pro.3956

Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] Stallmach R, Kavishwar M, Withers-Martinez C, Hackett F, Collins CR, Howell SA, Yeoh S, Knuepfer E, Atid AJ, Holder AA, Blackman MJ. Plasmodium falciparum SERA5 plays a non-enzymatic role in the malarial asexual blood-stage lifecycle. Mol Microbiol. 2015 Apr;96(2):368-87. PMID:25599609 doi:10.1111/mmi.12941

[2] Collins CR, Hackett F, Atid J, Tan MSY, Blackman MJ. The Plasmodium falciparum pseudoprotease SERA5 regulates the kinetics and efficiency of malaria parasite egress from host erythrocytes. PLoS Pathog. 2017 Jul 6;13(7):e1006453. PMID:28683142 doi:10.1371/journal.ppat.1006453

[3] Hodder AN, Drew DR, Epa VC, Delorenzi M, Bourgon R, Miller SK, Moritz RL, Frecklington DF, Simpson RJ, Speed TP, Pike RN, Crabb BS. Enzymic, phylogenetic, and structural characterization of the unusual papain-like protease domain of Plasmodium falciparum SERA5. J Biol Chem. 2003 Nov 28;278(48):48169-77. PMID:13679369 doi:10.1074/jbc.M306755200

[4] Kanodia S, Kumar G, Rizzi L, Pedretti A, Hodder AN, Romeo S, Malhotra P. Synthetic peptides derived from the C-terminal 6kDa region of Plasmodium falciparum SERA5 inhibit the enzyme activity and malaria parasite development. Biochim Biophys Acta. 2014 Sep;1840(9):2765-75. PMID:24769454 doi:10.1016/j.bbagen.2014.04.013

[5] Stallmach R, Kavishwar M, Withers-Martinez C, Hackett F, Collins CR, Howell SA, Yeoh S, Knuepfer E, Atid AJ, Holder AA, Blackman MJ. Plasmodium falciparum SERA5 plays a non-enzymatic role in the malarial asexual blood-stage lifecycle. Mol Microbiol. 2015 Apr;96(2):368-87. PMID:25599609 doi:10.1111/mmi.12941

[6] Iyer GR, Singh S, Kaur I, Agarwal S, Siddiqui MA, Bansal A, Kumar G, Saini E, Paul G, Mohmmed A, Chitnis CE, Malhotra P. Calcium-dependent phosphorylation of Plasmodium falciparum serine repeat antigen 5 triggers merozoite egress. J Biol Chem. 2018 Jun 22;293(25):9736-9746. PMID:29716996 doi:10.1074/jbc.RA117.001540

[7] Smith NA, Clarke OB, Lee M, Hodder AN, Smith BJ. Structure of the Plasmodium falciparum PfSERA5 pseudo-zymogen. Protein Sci. 2020 Sep 21. doi: 10.1002/pro.3956. PMID:32955133 doi:https://dx.doi.org/10.1002/pro.3956

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@@ Line 3: / Line 3: @@
 <StructureSection load='6x44' size='340' side='right'caption='[[6x44]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6x44]] is a 2 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=6X44 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6X44 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6x44]] is a 2 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=6X44 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6X44 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene></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]] 2.1973395&#8491;</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">sera5 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=5833 PLAFA])</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6x44 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6x44 OCA], [http://pdbe.org/6x44 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6x44 RCSB], [http://www.ebi.ac.uk/pdbsum/6x44 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6x44 ProSAT]</span></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=6x44 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6x44 OCA], [https://pdbe.org/6x44 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6x44 RCSB], [https://www.ebi.ac.uk/pdbsum/6x44 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6x44 ProSAT]</span></td></tr>
 </table>
+== Function ==
+[https://www.uniprot.org/uniprot/SERA5_PLAF7 SERA5_PLAF7] Plays an essential role during the asexual blood stage development by controlling the kinetics of merozoite egress from host erythrocytes (PubMed:25599609, PubMed:28683142). Specifically, prevents premature rupture of the parasitophorous vacuole and host erythrocyte membranes (PubMed:28683142).<ref>PMID:25599609</ref> <ref>PMID:28683142</ref>   May prevent merozoite phagocytosis by host monocytes via interaction with host VTN at the merozoite surface (By similarity). Plays a role in parasite growth (By similarity).[UniProtKB:P69193]  Protease activity is controversial (PubMed:25599609). Has been shown in a number of studies to have protease activity towards a synthetic peptide in vitro (PubMed:13679369, PubMed:24769454, PubMed:29716996). Has also been shown to lack protease activity towards a synthetic peptide in vitro (PubMed:25599609).<ref>PMID:13679369</ref> <ref>PMID:24769454</ref> <ref>PMID:25599609</ref> <ref>PMID:29716996</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 22: / Line 24: @@
 </StructureSection>
 [[Category: Large Structures]]
-[[Category: Plafa]]
+[[Category: Plasmodium falciparum]]
-[[Category: Clarke, O B]]
+[[Category: Clarke OB]]
-[[Category: Lee, M]]
+[[Category: Lee M]]
-[[Category: Smith, B J]]
+[[Category: Smith BJ]]
-[[Category: Smith, N A]]
+[[Category: Smith NA]]
-[[Category: Hydrolase]]
-[[Category: Malaria]]
-[[Category: Prodomain]]
-[[Category: Protease]]

6x44: Difference between revisions

Latest revision as of 14:41, 18 October 2023

High Resolution Crystal Structure Analysis of SERA5 proenzyme from plasmodium falciparum

Structural highlights

Function

Publication Abstract from PubMed

References

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