2ch1

From Proteopedia

(Difference between revisions)

Current revision

Structure of Anopheles gambiae 3-hydroxykynurenine transaminase

Structural highlights

2ch1 is a 4 chain structure with sequence from Anopheles gambiae. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.4Å
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

HKT_ANOGA Catalyzes the pyridoxal 5'-phosphate-dependent transamination of both 3-hydroxykynurenine and L-kynurenine to xanthurenic acid and kynurenic acid, respectively, preferentially using the alpha-ketoacid glyoxylate as the amino group acceptor (PubMed:16262702). Although glyoxylate is the preferred amino group acceptor, transamination of 3-hydroxykynurenine also works with pyruvate as the amino acceptor in vitro (PubMed:16262702). Involved in the detoxification of cytotoxic metabolite 3-hydroxykynurenine generated by the hydroxylation of L-kynurenine, an intermediate in the tryptophan catabolism pathway (PubMed:16262702). The Plasmodium parasite uses xanthurenic acid produced in the midgut to activate its gametocytes ingested during a blood meal (Probable). Also catalyzes, although with a lesser efficiency, the transamination of alanine with glyoxylate as an amino group acceptor (By similarity). May play a role in the detoxification of glyoxylate, a toxic plant metabolite from the diet (By similarity).[UniProtKB:Q0IG34]^[1] ^[2]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

In Anopheles gambiae, the vector for the most deadly malaria parasite Plasmodium falciparum, xanthurenic acid (XA) plays a key role in parasite gametogenesis and fertility. In mosquitoes, XA is produced by transamination of 3-hydroxykynurenine (3-HK), a reaction that represents the main route to prevent the accumulation of the potentially toxic 3-HK excess. Interfering with XA metabolism in A. gambiae therefore appears an attractive avenue for the development of malaria transmission-blocking drugs and insecticides. We have determined the crystal structure of A. gambiae 3-HK transaminase in its pyridoxal 5'-phosphate form and in complex with a newly synthesized competitive enzyme inhibitor. Structural inspection of the enzyme active site reveals the key molecular determinants for ligand recognition and catalysis. Major contributions toward inhibitor binding are provided by a salt bridge between the inhibitor carboxylate and Arg-356 and by a remarkable hydrogen bond network involving the anthranilic moiety of the inhibitor and backbone atoms of residues Gly-25 and Asn-44. This study may be useful for the structure-based design of specific enzyme inhibitors of potential interest as antimalarial agents.

Crystal structure of the Anopheles gambiae 3-hydroxykynurenine transaminase.,Rossi F, Garavaglia S, Giovenzana GB, Arca B, Li J, Rizzi M Proc Natl Acad Sci U S A. 2006 Apr 11;103(15):5711-6. Epub 2006 Apr 3. PMID:16585514^[3]

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

References

↑ Rossi F, Lombardo F, Paglino A, Cassani C, Miglio G, Arcà B, Rizzi M. Identification and biochemical characterization of the Anopheles gambiae 3-hydroxykynurenine transaminase. FEBS J. 2005 Nov;272(21):5653-62. PMID:16262702 doi:10.1111/j.1742-4658.2005.04961.x
↑ Rossi F, Lombardo F, Paglino A, Cassani C, Miglio G, Arcà B, Rizzi M. Identification and biochemical characterization of the Anopheles gambiae 3-hydroxykynurenine transaminase. FEBS J. 2005 Nov;272(21):5653-62. PMID:16262702 doi:10.1111/j.1742-4658.2005.04961.x
↑ Rossi F, Garavaglia S, Giovenzana GB, Arca B, Li J, Rizzi M. Crystal structure of the Anopheles gambiae 3-hydroxykynurenine transaminase. Proc Natl Acad Sci U S A. 2006 Apr 11;103(15):5711-6. Epub 2006 Apr 3. PMID:16585514

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2ch1"

@@ Line 1: / Line 1: @@
 ==Structure of Anopheles gambiae 3-hydroxykynurenine transaminase==
-<StructureSection load='2ch1' size='340' side='right' caption='[[2ch1]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
+<StructureSection load='2ch1' size='340' side='right'caption='[[2ch1]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2ch1]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Anopheles_gambiae Anopheles gambiae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2CH1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2CH1 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2ch1]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Anopheles_gambiae Anopheles gambiae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2CH1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2CH1 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=PLP:PYRIDOXAL-5-PHOSPHATE'>PLP</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]] 2.4&#8491;</td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2ch2|2ch2]]</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=PLP:PYRIDOXAL-5-PHOSPHATE'>PLP</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=2ch1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ch1 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2ch1 RCSB], [http://www.ebi.ac.uk/pdbsum/2ch1 PDBsum]</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=2ch1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ch1 OCA], [https://pdbe.org/2ch1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2ch1 RCSB], [https://www.ebi.ac.uk/pdbsum/2ch1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2ch1 ProSAT]</span></td></tr>
 </table>
+== Function ==
+[https://www.uniprot.org/uniprot/HKT_ANOGA HKT_ANOGA] Catalyzes the pyridoxal 5'-phosphate-dependent transamination of both 3-hydroxykynurenine and L-kynurenine to xanthurenic acid and kynurenic acid, respectively, preferentially using the alpha-ketoacid glyoxylate as the amino group acceptor (PubMed:16262702). Although glyoxylate is the preferred amino group acceptor, transamination of 3-hydroxykynurenine also works with pyruvate as the amino acceptor in vitro (PubMed:16262702). Involved in the detoxification of cytotoxic metabolite 3-hydroxykynurenine generated by the hydroxylation of L-kynurenine, an intermediate in the tryptophan catabolism pathway (PubMed:16262702). The Plasmodium parasite uses xanthurenic acid produced in the midgut to activate its gametocytes ingested during a blood meal (Probable). Also catalyzes, although with a lesser efficiency, the transamination of alanine with glyoxylate as an amino group acceptor (By similarity). May play a role in the detoxification of glyoxylate, a toxic plant metabolite from the diet (By similarity).[UniProtKB:Q0IG34]<ref>PMID:16262702</ref> <ref>PMID:16262702</ref>
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ch/2ch1_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ch/2ch1_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
   </jmolCheckbox>
-</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf].
+</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2ch1 ConSurf].
 <div style="clear:both"></div>
 <div style="background-color:#fffaf0;">
@@ Line 25: / Line 28: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 2ch1" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>
@@ Line 30: / Line 34: @@
 </StructureSection>
 [[Category: Anopheles gambiae]]
-[[Category: Arca, B]]
+[[Category: Large Structures]]
-[[Category: Garavaglia, S]]
+[[Category: Arca B]]
-[[Category: Giovenzana, G B]]
+[[Category: Garavaglia S]]
-[[Category: Li, J]]
+[[Category: Giovenzana GB]]
-[[Category: Rizzi, M]]
+[[Category: Li J]]
-[[Category: Rossi, F]]
+[[Category: Rizzi M]]
-[[Category: 3-hydroxykynurenine transaminase]]
+[[Category: Rossi F]]
-[[Category: Kynurenine pathway]]
-[[Category: Plp-enzyme]]
-[[Category: Transferase]]

2ch1

From Proteopedia

Current revision

Structure of Anopheles gambiae 3-hydroxykynurenine transaminase

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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