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4r5t

From Proteopedia

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Current revision

Structure of the m1 alanylaminopeptidase from malaria complexed with a hydroxamic acid-based inhibitor

Structural highlights

4r5t 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.
Method:	X-ray diffraction, Resolution 1.98Å
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

Plasmodium parasites, the causative agents of malaria, have developed resistance to most of our current antimalarial therapies, including artemisinin combination therapies which are widely described as our last line of defense. Antimalarial agents with a novel mode of action are urgently required. Two Plasmodium falciparum aminopeptidases, PfA-M1 and PfA-M17, play crucial roles in the erythrocytic stage of infection and have been validated as potential antimalarial targets. Using compound-bound crystal structures of both enzymes, we have used a structure-guided approach to develop a novel series of inhibitors capable of potent inhibition of both PfA-M1 and PfA-M17 activity and parasite growth in culture. Herein we describe the design, synthesis, and evaluation of a series of hydroxamic acid-based inhibitors and demonstrate the compounds to be exciting new leads for the development of novel antimalarial therapeutics.

Two-Pronged Attack: Dual Inhibition of Plasmodium falciparum M1 and M17 Metalloaminopeptidases by a Novel Series of Hydroxamic Acid-Based Inhibitors.,Mistry SN, Drinkwater N, Ruggeri C, Sivaraman KK, Loganathan S, Fletcher S, Drag M, Paiardini A, Avery VM, Scammells PJ, McGowan S J Med Chem. 2014 Oct 24. PMID:25299353^[3]

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

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
↑ Mistry SN, Drinkwater N, Ruggeri C, Sivaraman KK, Loganathan S, Fletcher S, Drag M, Paiardini A, Avery VM, Scammells PJ, McGowan S. Two-Pronged Attack: Dual Inhibition of Plasmodium falciparum M1 and M17 Metalloaminopeptidases by a Novel Series of Hydroxamic Acid-Based Inhibitors. J Med Chem. 2014 Oct 24. PMID:25299353 doi:http://dx.doi.org/10.1021/jm501323a

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4r5t"

Categories: Large Structures | Plasmodium falciparum FcB1/Columbia | Drinkwater N | Mcgowan S

@@ Line 3: / Line 3: @@
 <StructureSection load='4r5t' size='340' side='right'caption='[[4r5t]], [[Resolution|resolution]] 1.98&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4r5t]] 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=4R5T OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4R5T FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4r5t]] 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=4R5T OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4R5T FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=R5T:TERT-BUTYL+{(1S)-2-(HYDROXYAMINO)-2-OXO-1-[4-(1H-PYRAZOL-1-YL)PHENYL]ETHYL}CARBAMATE'>R5T</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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]] 1.98&#8491;</td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3ebg|3ebg]], [[4r5v|4r5v]], [[4r5x|4r5x]], [[4r6t|4r6t]], [[4r76|4r76]], [[4r7m|4r7m]]</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=R5T:TERT-BUTYL+{(1S)-2-(HYDROXYAMINO)-2-OXO-1-[4-(1H-PYRAZOL-1-YL)PHENYL]ETHYL}CARBAMATE'>R5T</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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4r5t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4r5t OCA], [http://pdbe.org/4r5t PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4r5t RCSB], [http://www.ebi.ac.uk/pdbsum/4r5t PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4r5t 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=4r5t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4r5t OCA], [https://pdbe.org/4r5t PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4r5t RCSB], [https://www.ebi.ac.uk/pdbsum/4r5t PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4r5t ProSAT]</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>
+[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;">
 == Publication Abstract from PubMed ==
@@ Line 27: / Line 27: @@
 </StructureSection>
 [[Category: Large Structures]]
-[[Category: Plafq]]
+[[Category: Plasmodium falciparum FcB1/Columbia]]
-[[Category: Drinkwater, N]]
+[[Category: Drinkwater N]]
-[[Category: Mcgowan, S]]
+[[Category: Mcgowan S]]
-[[Category: Hydrolase-hydrolase inhibitor complex]]
-[[Category: Protease]]

4r5t

From Proteopedia

Current revision

Structure of the m1 alanylaminopeptidase from malaria complexed with a hydroxamic acid-based inhibitor

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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