4x2u: Difference between revisions

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<StructureSection load='4x2u' size='340' side='right'caption='[[4x2u]], [[Resolution|resolution]] 1.50&Aring;' scene=''>
<StructureSection load='4x2u' size='340' side='right'caption='[[4x2u]], [[Resolution|resolution]] 1.50&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[4x2u]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Plafq Plafq]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4X2U OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4X2U FirstGlance]. <br>
<table><tr><td colspan='2'>[[4x2u]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Plasmodium_falciparum_FcB1/Columbia Plasmodium falciparum FcB1/Columbia]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4X2U OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4X2U FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=TOD:(2S)-({(2R)-2-[(1S)-1-HYDROXY-2-(HYDROXYAMINO)-2-OXOETHYL]-4-METHYLPENTANOYL}AMINO)(PHENYL)ETHANOIC+ACID'>TOD</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=TOD:(2S)-({(2R)-2-[(1S)-1-HYDROXY-2-(HYDROXYAMINO)-2-OXOETHYL]-4-METHYLPENTANOYL}AMINO)(PHENYL)ETHANOIC+ACID'>TOD</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3ebg|3ebg]], [[3ebh|3ebh]], [[4x2t|4x2t]]</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=4x2u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4x2u OCA], [https://pdbe.org/4x2u PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4x2u RCSB], [https://www.ebi.ac.uk/pdbsum/4x2u PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4x2u 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=4x2u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4x2u OCA], [http://pdbe.org/4x2u PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4x2u RCSB], [http://www.ebi.ac.uk/pdbsum/4x2u PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4x2u ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
[[http://www.uniprot.org/uniprot/AMP1_PLAFQ AMP1_PLAFQ]] Displays aminopeptidase activity with a broad substrate specificity. Preferentially hydrolyzes L-Lys-AMC but also shows strong activity against L-Ala-AMC, L-Arg-AMC and L-Leu-AMC.<ref>PMID:12166515</ref> <ref>PMID:19196988</ref>
[https://www.uniprot.org/uniprot/AMP1_PLAFQ AMP1_PLAFQ] Displays aminopeptidase activity with a broad substrate specificity. Preferentially hydrolyzes L-Lys-AMC but also shows strong activity against L-Ala-AMC, L-Arg-AMC and L-Leu-AMC.<ref>PMID:12166515</ref> <ref>PMID:19196988</ref>  
<div style="background-color:#fffaf0;">
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
== Publication Abstract from PubMed ==
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</StructureSection>
</StructureSection>
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Plafq]]
[[Category: Plasmodium falciparum FcB1/Columbia]]
[[Category: Drinkwater, N]]
[[Category: Drinkwater N]]
[[Category: McGowan, S]]
[[Category: McGowan S]]
[[Category: Antimalarial]]
[[Category: Hydrolase-hydrolase inhibitor complex]]
[[Category: Inhibitor]]
[[Category: M1 alanyl-aminopeptidase]]
[[Category: Plasmodium falciparum]]
[[Category: Protease]]
[[Category: Tosedostat]]

Revision as of 00:08, 13 April 2023

X-ray crystal structure of the orally available aminopeptidase inhibitor, Tosedostat, bound to the M1 Alanyl Aminopeptidase from P. falciparumX-ray crystal structure of the orally available aminopeptidase inhibitor, Tosedostat, bound to the M1 Alanyl Aminopeptidase from P. falciparum

Structural highlights

4x2u is a 1 chain structure with sequence from Plasmodium falciparum FcB1/Columbia. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:, , ,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

AMP1_PLAFQ Displays aminopeptidase activity with a broad substrate specificity. Preferentially hydrolyzes L-Lys-AMC but also shows strong activity against L-Ala-AMC, L-Arg-AMC and L-Leu-AMC.[1] [2]

Publication Abstract from PubMed

New antimalarial treatments are desperately required to face the spread of drug resistant parasites. Inhibition of metalloaminopeptidases PfA-M1 and PfA-M17 is a validated therapeutic strategy for treatment of Plasmodium falciparum malaria. Here we describe the crystal structures of PfA-M1 and PfA-M17 bound to chemotherapeutic agent Tosedostat. The inhibitor occupies the enzymes' putative product egress channels in addition to the substrate binding pockets; however, adopts different binding poses when bound to PfA-M1 and PfA-M17. These findings will be valuable for the continued development of selective inhibitors of PfA-M1 and PfA-M17. This article is protected by copyright. All rights reserved.

X-ray crystal structures of an orally available aminopeptidase inhibitor, Tosedostat, bound to anti-malarial drug targets PfA-M1 and PfA-M17.,Drinkwater N, Bamert RS, Kannan Sivaraman K, Paiardini A, McGowan S Proteins. 2015 Feb 2. doi: 10.1002/prot.24771. PMID:25645579[3]

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

See Also

References

  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. ↑ Drinkwater N, Bamert RS, Kannan Sivaraman K, Paiardini A, McGowan S. X-ray crystal structures of an orally available aminopeptidase inhibitor, Tosedostat, bound to anti-malarial drug targets PfA-M1 and PfA-M17. Proteins. 2015 Feb 2. doi: 10.1002/prot.24771. PMID:25645579 doi:http://dx.doi.org/10.1002/prot.24771

4x2u, resolution 1.50Å

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