This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.

Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.


3q44

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Current revision (11:33, 14 March 2024) (edit) (undo)
 
Line 3: Line 3:
<StructureSection load='3q44' size='340' side='right'caption='[[3q44]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
<StructureSection load='3q44' size='340' side='right'caption='[[3q44]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
-
<table><tr><td colspan='2'>[[3q44]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Plafq Plafq]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3Q44 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3Q44 FirstGlance]. <br>
+
<table><tr><td colspan='2'>[[3q44]] 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=3Q44 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3Q44 FirstGlance]. <br>
-
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=D50:N-{(2S,3R)-3-AMINO-4-[4-(BENZYLOXY)PHENYL]-2-HYDROXYBUTANOYL}-L-LEUCINE'>D50</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>
+
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.8&#8491;</td></tr>
-
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3q43|3q43]]</div></td></tr>
+
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=D50:N-{(2S,3R)-3-AMINO-4-[4-(BENZYLOXY)PHENYL]-2-HYDROXYBUTANOYL}-L-LEUCINE'>D50</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=3q44 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3q44 OCA], [https://pdbe.org/3q44 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3q44 RCSB], [https://www.ebi.ac.uk/pdbsum/3q44 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3q44 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=3q44 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3q44 OCA], [https://pdbe.org/3q44 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3q44 RCSB], [https://www.ebi.ac.uk/pdbsum/3q44 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3q44 ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
-
[[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>
+
[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 ==
+
-
The malarial PfA-M1 metallo-aminopeptidase is considered a putative drug target. The natural product dipeptide mimetic, bestatin, is a potent inhibitor of PfA-M1. Herein we present a new, efficient, and high-yielding protocol for the synthesis of bestatin derivatives from natural and unnatural N-Boc-d-amino acids. A diverse library of bestatin derivatives was synthesized with variants at the side chain of either the alpha-hydroxy-beta-amino acid (P1) or the adjacent natural alpha-amino acid (P1'). Surprisingly, we found that extended aromatic side chains at the P1 position resulted in potent inhibition against PfA-M1. To understand these data, we determined the X-ray cocrystal structures of PfA-M1 with two derivatives having either a Tyr(OMe) 15 or Tyr(OBzl) 16 at the P1 position and observed substantial inhibitor-induced rearrangement of the primary loop within the PfA-M1 pocket that interacts with the P1 side chain. Our data provide important insights for the rational design of more potent and selective inhibitors of this enzyme that may eventually lead to new therapies for malaria.
+
-
 
+
-
Synthesis of New (-)-Bestatin-Based Inhibitor Libraries Reveals a Novel Binding Mode in the S1 Pocket of the Essential Malaria M1 Metalloaminopeptidase.,Velmourougane G, Harbut MB, Dalal S, McGowan S, Oellig CA, Meinhardt N, Whisstock JC, Klemba M, Greenbaum DC J Med Chem. 2011 Mar 2. PMID:21366301<ref>PMID:21366301</ref>
+
-
 
+
-
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+
-
</div>
+
-
<div class="pdbe-citations 3q44" style="background-color:#fffaf0;"></div>
+
==See Also==
==See Also==
Line 27: Line 18:
</StructureSection>
</StructureSection>
[[Category: Large Structures]]
[[Category: Large Structures]]
-
[[Category: Plafq]]
+
[[Category: Plasmodium falciparum FcB1/Columbia]]
-
[[Category: Greenbaum, D C]]
+
[[Category: Greenbaum DC]]
-
[[Category: McGowan, S]]
+
[[Category: McGowan S]]
-
[[Category: Hydrolase-hydrolase inhibitor complex]]
+
-
[[Category: M1 aminopeptidase]]
+

Current revision

X-ray crystal structure of PfA-M1 bound to Bestatin derivative 16

PDB ID 3q44

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3q44"
Personal tools