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{{STRUCTURE_4k5o|  PDB=4k5o  |  SCENE=  }}
==Phosphonic Arginine Mimetics as Inhibitors of the M1 Aminopeptidases from Plasmodium falciparum==
===Phosphonic Arginine Mimetics as Inhibitors of the M1 Aminopeptidases from Plasmodium falciparum===
<StructureSection load='4k5o' size='340' side='right' caption='[[4k5o]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
{{ABSTRACT_PUBMED_23713488}}
== Structural highlights ==
<table><tr><td colspan='2'>[[4k5o]] is a 1 chain structure with sequence from [http://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=4K5O OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4K5O FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1OT:{(R)-AMINO[4-(1H-PYRAZOL-1-YL)PHENYL]METHYL}PHOSPHONIC+ACID'>1OT</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='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4k5l|4k5l]], [[4k5m|4k5m]], [[4k5n|4k5n]], [[4k3n|4k3n]], [[4k5p|4k5p]]</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=4k5o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4k5o OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4k5o RCSB], [http://www.ebi.ac.uk/pdbsum/4k5o PDBsum]</span></td></tr>
</table>
== 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> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The malaria parasite &lt;i&gt;Plasmodium falciparum&lt;/i&gt; employs two metallo-aminopeptidases, P&lt;i&gt;f&lt;/i&gt;A-M1 and P&lt;I&gt;f&lt;/i&gt;A-M17, which are essential for parasite survival. Compounds that inhibit the activity of either enzyme represent leads for the development of new anti-malarial drugs. Here we report the synthesis and structure-activity-relationships of a small library of phosphonic acid arginine mimetics that probe the S1 pocket of both enzymes, and map the necessary interactions that would be important for a dual inhibitor.


==Function==
Synthesis and Structure-Activity Relationships of Phosphonic Arginine Mimetics as Inhibitors of the M1 and M17 Aminopeptidases from &lt;i&gt;Plasmodium falciparum&lt;/i&gt;,Kannan Sivaraman K, Paiardini A, Sienczyk M, Ruggeri C, Oellig CA, Dalton JP, Scammells PJ, Drag M, McGowan S J Med Chem. 2013 May 28. PMID:23713488<ref>PMID:23713488</ref>
[[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>


==About this Structure==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
[[4k5o]] is a 1 chain structure with sequence from [http://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=4K5O OCA].
</div>


==Reference==
==See Also==
<ref group="xtra">PMID:023713488</ref><references group="xtra"/><references/>
*[[Aminopeptidase|Aminopeptidase]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Plasmodium falciparum fcb1/columbia]]
[[Category: Plasmodium falciparum fcb1/columbia]]
[[Category: McGowan, S.]]
[[Category: McGowan, S]]
[[Category: Hydrolase-hydrolase inhibitor complex]]
[[Category: Hydrolase-hydrolase inhibitor complex]]
[[Category: M1 alanyl-aminopeptidase]]
[[Category: M1 alanyl-aminopeptidase]]
[[Category: Protease]]
[[Category: Protease]]

Revision as of 17:10, 25 December 2014

Phosphonic Arginine Mimetics as Inhibitors of the M1 Aminopeptidases from Plasmodium falciparumPhosphonic Arginine Mimetics as Inhibitors of the M1 Aminopeptidases from Plasmodium falciparum

Structural highlights

4k5o 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, RCSB, PDBsum

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

The malaria parasite <i>Plasmodium falciparum</i> employs two metallo-aminopeptidases, P<i>f</i>A-M1 and P<I>f</i>A-M17, which are essential for parasite survival. Compounds that inhibit the activity of either enzyme represent leads for the development of new anti-malarial drugs. Here we report the synthesis and structure-activity-relationships of a small library of phosphonic acid arginine mimetics that probe the S1 pocket of both enzymes, and map the necessary interactions that would be important for a dual inhibitor.

Synthesis and Structure-Activity Relationships of Phosphonic Arginine Mimetics as Inhibitors of the M1 and M17 Aminopeptidases from <i>Plasmodium falciparum</i>,Kannan Sivaraman K, Paiardini A, Sienczyk M, Ruggeri C, Oellig CA, Dalton JP, Scammells PJ, Drag M, McGowan S J Med Chem. 2013 May 28. PMID:23713488[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. ↑ Kannan Sivaraman K, Paiardini A, Sienczyk M, Ruggeri C, Oellig CA, Dalton JP, Scammells PJ, Drag M, McGowan S. Synthesis and Structure-Activity Relationships of Phosphonic Arginine Mimetics as Inhibitors of the M1 and M17 Aminopeptidases from Plasmodium falciparum J Med Chem. 2013 May 28. PMID:23713488 doi:10.1021/jm4005972

4k5o, resolution 1.90Å

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