8slo: Difference between revisions

Revision as of 05:50, 3 April 2024

Plasmodium falciparum M1 aminopeptidase bound to selective inhibitor MIPS2673

Structural highlights

8slo is a 1 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 1.55Å
Ligands:	BYW, GOL, MG, ZN
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

AMPN_PLAF7 Displays aminopeptidase activity with a broad substrate specificity (PubMed:9879894, PubMed:12166515, PubMed:21659511, PubMed:22359643, PubMed:34133730, PubMed:33536500, PubMed:19196988, PubMed:21844374, PubMed:23897806). Preferentially, cleaves after Leu and Met, but cleaves also after Ala and Arg (PubMed:12166515, PubMed:22359643, PubMed:33536500, PubMed:21844374). Low activity towards Lys, Phe, Tyr, Trp, Gln, Ser and Gly and negligible activity towards Glu, Asp, Pro, Ile, Thr, Val, His and Asn (PubMed:22359643). Has dipeptidase activity (PubMed:21659511, PubMed:23897806). Plays a role in the terminal stages of host hemoglobin digestion by cleaving the N-terminal residue of small hemoglobin-derived oligopeptides (PubMed:21659511, PubMed:34133730, PubMed:21844374).^[1] ^[2] ^[3] ^[4] ^[5] ^[6] ^[7] ^[8] ^[9]

References

↑ Allary M, Schrevel J, Florent I. Properties, stage-dependent expression and localization of Plasmodium falciparum M1 family zinc-aminopeptidase. Parasitology. 2002 Jul;125(Pt 1):1-10. PMID:12166515
↑ McGowan S, Porter CJ, Lowther J, Stack CM, Golding SJ, Skinner-Adams TS, Trenholme KR, Teuscher F, Donnelly SM, Grembecka J, Mucha A, Kafarski P, Degori R, Buckle AM, Gardiner DL, Whisstock JC, Dalton JP. Structural basis for the inhibition of the essential Plasmodium falciparum M1 neutral aminopeptidase. Proc Natl Acad Sci U S A. 2009 Feb 5. PMID:19196988
↑ Ragheb D, Dalal S, Bompiani KM, Ray WK, Klemba M. Distribution and biochemical properties of an M1-family aminopeptidase in Plasmodium falciparum indicate a role in vacuolar hemoglobin catabolism. J Biol Chem. 2011 Aug 5;286(31):27255-65. PMID:21659511 doi:10.1074/jbc.M111.225318
↑ Harbut MB, Velmourougane G, Dalal S, Reiss G, Whisstock JC, Onder O, Brisson D, McGowan S, Klemba M, Greenbaum DC. Bestatin-based chemical biology strategy reveals distinct roles for malaria M1- and M17-family aminopeptidases. Proc Natl Acad Sci U S A. 2011 Aug 23;108(34):E526-34. Epub 2011 Aug 15. PMID:21844374 doi:10.1073/pnas.1105601108
↑ Poreba M, McGowan S, Skinner-Adams TS, Trenholme KR, Gardiner DL, Whisstock JC, To J, Salvesen GS, Dalton JP, Drag M. Fingerprinting the substrate specificity of M1 and M17 aminopeptidases of human malaria, Plasmodium falciparum. PLoS One. 2012;7(2):e31938. PMID:22359643 doi:10.1371/journal.pone.0031938
↑ Dalal S, Ragheb DR, Schubot FD, Klemba M. A naturally variable residue in the S1 subsite of M1-family aminopeptidases modulates catalytic properties and promotes functional specialization. J Biol Chem. 2013 Jul 29. PMID:23897806 doi:10.1074/jbc.M113.465625
↑ Mathew R, Wunderlich J, Thivierge K, Cwiklinski K, Dumont C, Tilley L, Rohrbach P, Dalton JP. Biochemical and cellular characterisation of the Plasmodium falciparum M1 alanyl aminopeptidase (PfM1AAP) and M17 leucyl aminopeptidase (PfM17LAP). Sci Rep. 2021 Feb 3;11(1):2854. PMID:33536500 doi:10.1038/s41598-021-82499-4
↑ Malcolm TR, Swiderska KW, Hayes BK, Webb CT, Drag M, Drinkwater N, McGowan S. Mapping the substrate specificity of the Plasmodium M1 and M17 aminopeptidases. Biochem J. 2021 Jul 16;478(13):2697-2713. PMID:34133730 doi:10.1042/BCJ20210172
↑ Florent I, Derhy Z, Allary M, Monsigny M, Mayer R, Schrével J. A Plasmodium falciparum aminopeptidase gene belonging to the M1 family of zinc-metallopeptidases is expressed in erythrocytic stages. Mol Biochem Parasitol. 1998 Nov 30;97(1-2):149-60. PMID:9879894 doi:10.1016/s0166-6851(98)00143-1

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OCA

[1] Allary M, Schrevel J, Florent I. Properties, stage-dependent expression and localization of Plasmodium falciparum M1 family zinc-aminopeptidase. Parasitology. 2002 Jul;125(Pt 1):1-10. PMID:12166515

[2] McGowan S, Porter CJ, Lowther J, Stack CM, Golding SJ, Skinner-Adams TS, Trenholme KR, Teuscher F, Donnelly SM, Grembecka J, Mucha A, Kafarski P, Degori R, Buckle AM, Gardiner DL, Whisstock JC, Dalton JP. Structural basis for the inhibition of the essential Plasmodium falciparum M1 neutral aminopeptidase. Proc Natl Acad Sci U S A. 2009 Feb 5. PMID:19196988

[3] Ragheb D, Dalal S, Bompiani KM, Ray WK, Klemba M. Distribution and biochemical properties of an M1-family aminopeptidase in Plasmodium falciparum indicate a role in vacuolar hemoglobin catabolism. J Biol Chem. 2011 Aug 5;286(31):27255-65. PMID:21659511 doi:10.1074/jbc.M111.225318

[4] Harbut MB, Velmourougane G, Dalal S, Reiss G, Whisstock JC, Onder O, Brisson D, McGowan S, Klemba M, Greenbaum DC. Bestatin-based chemical biology strategy reveals distinct roles for malaria M1- and M17-family aminopeptidases. Proc Natl Acad Sci U S A. 2011 Aug 23;108(34):E526-34. Epub 2011 Aug 15. PMID:21844374 doi:10.1073/pnas.1105601108

[5] Poreba M, McGowan S, Skinner-Adams TS, Trenholme KR, Gardiner DL, Whisstock JC, To J, Salvesen GS, Dalton JP, Drag M. Fingerprinting the substrate specificity of M1 and M17 aminopeptidases of human malaria, Plasmodium falciparum. PLoS One. 2012;7(2):e31938. PMID:22359643 doi:10.1371/journal.pone.0031938

[6] Dalal S, Ragheb DR, Schubot FD, Klemba M. A naturally variable residue in the S1 subsite of M1-family aminopeptidases modulates catalytic properties and promotes functional specialization. J Biol Chem. 2013 Jul 29. PMID:23897806 doi:10.1074/jbc.M113.465625

[7] Mathew R, Wunderlich J, Thivierge K, Cwiklinski K, Dumont C, Tilley L, Rohrbach P, Dalton JP. Biochemical and cellular characterisation of the Plasmodium falciparum M1 alanyl aminopeptidase (PfM1AAP) and M17 leucyl aminopeptidase (PfM17LAP). Sci Rep. 2021 Feb 3;11(1):2854. PMID:33536500 doi:10.1038/s41598-021-82499-4

[8] Malcolm TR, Swiderska KW, Hayes BK, Webb CT, Drag M, Drinkwater N, McGowan S. Mapping the substrate specificity of the Plasmodium M1 and M17 aminopeptidases. Biochem J. 2021 Jul 16;478(13):2697-2713. PMID:34133730 doi:10.1042/BCJ20210172

[9] Florent I, Derhy Z, Allary M, Monsigny M, Mayer R, Schrével J. A Plasmodium falciparum aminopeptidase gene belonging to the M1 family of zinc-metallopeptidases is expressed in erythrocytic stages. Mol Biochem Parasitol. 1998 Nov 30;97(1-2):149-60. PMID:9879894 doi:10.1016/s0166-6851(98)00143-1

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@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 8slo is ON HOLD  until Paper Publication
+==Plasmodium falciparum M1 aminopeptidase bound to selective inhibitor MIPS2673==
+<StructureSection load='8slo' size='340' side='right'caption='[[8slo]], [[Resolution|resolution]] 1.55&Aring;' scene=''>
-Authors:
+== Structural highlights ==
+<table><tr><td colspan='2'>[[8slo]] 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=8SLO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8SLO FirstGlance]. <br>
-Description:
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.55&#8491;</td></tr>
-[[Category: Unreleased Structures]]
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BYW:2-hydroxy-N-[(1R)-2-(hydroxyamino)-2-oxo-1-(3,4,5-trifluoro[1,1-biphenyl]-4-yl)ethyl]-2-methylpropanamide'>BYW</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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=8slo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8slo OCA], [https://pdbe.org/8slo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8slo RCSB], [https://www.ebi.ac.uk/pdbsum/8slo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8slo ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/AMPN_PLAF7 AMPN_PLAF7] Displays aminopeptidase activity with a broad substrate specificity (PubMed:9879894, PubMed:12166515, PubMed:21659511, PubMed:22359643, PubMed:34133730, PubMed:33536500, PubMed:19196988, PubMed:21844374, PubMed:23897806). Preferentially, cleaves after Leu and Met, but cleaves also after Ala and Arg (PubMed:12166515, PubMed:22359643, PubMed:33536500, PubMed:21844374). Low activity towards Lys, Phe, Tyr, Trp, Gln, Ser and Gly and negligible activity towards Glu, Asp, Pro, Ile, Thr, Val, His and Asn (PubMed:22359643). Has dipeptidase activity (PubMed:21659511, PubMed:23897806). Plays a role in the terminal stages of host hemoglobin digestion by cleaving the N-terminal residue of small hemoglobin-derived oligopeptides (PubMed:21659511, PubMed:34133730, PubMed:21844374).<ref>PMID:12166515</ref> <ref>PMID:19196988</ref> <ref>PMID:21659511</ref> <ref>PMID:21844374</ref> <ref>PMID:22359643</ref> <ref>PMID:23897806</ref> <ref>PMID:33536500</ref> <ref>PMID:34133730</ref> <ref>PMID:9879894</ref>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Large Structures]]
+[[Category: Plasmodium falciparum]]
+[[Category: Drinkwater N]]
+[[Category: McGowan SM]]

8slo: Difference between revisions

Revision as of 05:50, 3 April 2024

Plasmodium falciparum M1 aminopeptidase bound to selective inhibitor MIPS2673

Structural highlights

Function

References

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