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| | ==Structure of L-amino acid oxidase from the B. jararacussu venom== | | ==Structure of L-amino acid oxidase from the B. jararacussu venom== |
| - | <StructureSection load='4e0v' size='340' side='right' caption='[[4e0v]], [[Resolution|resolution]] 3.10Å' scene=''> | + | <StructureSection load='4e0v' size='340' side='right'caption='[[4e0v]], [[Resolution|resolution]] 3.10Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4e0v]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Bothrops_jararacussu Bothrops jararacussu]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4E0V OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4E0V FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4e0v]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Bothrops_jararacussu Bothrops jararacussu]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4E0V OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4E0V FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</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]] 3.1Å</td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/L-amino-acid_oxidase L-amino-acid oxidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.4.3.2 1.4.3.2] </span></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</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=4e0v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4e0v OCA], [http://pdbe.org/4e0v PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4e0v RCSB], [http://www.ebi.ac.uk/pdbsum/4e0v PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4e0v 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=4e0v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4e0v OCA], [https://pdbe.org/4e0v PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4e0v RCSB], [https://www.ebi.ac.uk/pdbsum/4e0v PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4e0v ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/OXLA1_BOTJR OXLA1_BOTJR] Catalyzes an oxidative deamination of predominantly hydrophobic and aromatic L-amino acids, thus producing hydrogen peroxide that may contribute to the diverse toxic effects of this enzyme (PubMed:22490662). Shows high specificity for L-Met, L-Leu, L-Phe, L-Tyr, L-Ile, L-Trp, a moderate activity on L-Cys and low activity on L-Val, L-Lys, L-Arg, L-His, L-Gln, L-Thr and L-Ser (PubMed:22490662). Exhibits diverse biological activities, such as hemorrhage, hemolysis, edema, apoptosis of vascular endothelial cells or tumor cell lines, and antibacterial, as well as regulation of platelet aggregation (By similarity). Effects of snake L-amino oxidases on platelets are controversial, since they either induce aggregation or inhibit agonist-induced aggregation (By similarity). These different effects are probably due to different experimental conditions (By similarity). In vitro, shows parasiticidal activities against both trypanosomes and leishmania, as a result of enzyme-catalyzed hydrogen peroxide production (PubMed:17292326).[UniProtKB:P0CC17]<ref>PMID:17292326</ref> <ref>PMID:22490662</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | | | |
| | ==See Also== | | ==See Also== |
| - | *[[Amino acid oxidase|Amino acid oxidase]] | + | *[[Amino acid oxidase 3D structures|Amino acid oxidase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Bothrops jararacussu]] | | [[Category: Bothrops jararacussu]] |
| - | [[Category: L-amino-acid oxidase]] | + | [[Category: Large Structures]] |
| - | [[Category: Arni, R K]] | + | [[Category: Arni RK]] |
| - | [[Category: Betzel, C]] | + | [[Category: Betzel C]] |
| - | [[Category: Murakami, M T]] | + | [[Category: Murakami MT]] |
| - | [[Category: Souza, T A.C B]] | + | [[Category: Souza TACB]] |
| - | [[Category: Ullah, A]] | + | [[Category: Ullah A]] |
| - | [[Category: Fad-binding mode]]
| + | |
| - | [[Category: L-amino acid oxidase]]
| + | |
| - | [[Category: Oxidoreductase]]
| + | |
| Structural highlights
Function
OXLA1_BOTJR Catalyzes an oxidative deamination of predominantly hydrophobic and aromatic L-amino acids, thus producing hydrogen peroxide that may contribute to the diverse toxic effects of this enzyme (PubMed:22490662). Shows high specificity for L-Met, L-Leu, L-Phe, L-Tyr, L-Ile, L-Trp, a moderate activity on L-Cys and low activity on L-Val, L-Lys, L-Arg, L-His, L-Gln, L-Thr and L-Ser (PubMed:22490662). Exhibits diverse biological activities, such as hemorrhage, hemolysis, edema, apoptosis of vascular endothelial cells or tumor cell lines, and antibacterial, as well as regulation of platelet aggregation (By similarity). Effects of snake L-amino oxidases on platelets are controversial, since they either induce aggregation or inhibit agonist-induced aggregation (By similarity). These different effects are probably due to different experimental conditions (By similarity). In vitro, shows parasiticidal activities against both trypanosomes and leishmania, as a result of enzyme-catalyzed hydrogen peroxide production (PubMed:17292326).[UniProtKB:P0CC17][1] [2]
Publication Abstract from PubMed
l-Amino acid oxidases (LAAOs) are flavoenzymes that catalytically deaminate l-amino acids to corresponding alpha-keto acids with the concomitant production of ammonia (NH(3)) and hydrogen peroxide (H(2)O(2)). Particularly, snake venom LAAOs have been attracted much attention due to their diverse clinical and biological effects, interfering on human coagulation factors and being cytotoxic against some pathogenic bacteria and Leishmania ssp. In this work, a new LAAO from Bothrops jararacussu venom (BjsuLAAO) was purified, functionally characterized and its structure determined by X-ray crystallography at 3.1A resolution. BjsuLAAO showed high catalytic specificity for aromatic and aliphatic large side-chain amino acids. Comparative structural analysis with prokaryotic LAAOs, which exhibit low specificity, indicates the importance of the active-site volume in modulating enzyme selectivity. Surprisingly, the flavin adenine dinucleotide (FAD) cofactor was found in a different orientation canonically described for both prokaryotic and eukaryotic LAAOs. In this new conformational state, the adenosyl group is flipped towards the 62-71 loop, being stabilized by several hydrogen-bond interactions, which is equally stable to the classical binding mode.
Structural insights into selectivity and cofactor binding in snake venom l-amino acid oxidases.,Ullah A, Souza TA, Abrego JR, Betzel C, Murakami MT, Arni RK Biochem Biophys Res Commun. 2012 Apr 3. PMID:22490662[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Franca SC, Kashima S, Roberto PG, Marins M, Ticli FK, Pereira JO, Astolfi-Filho S, Stabeli RG, Magro AJ, Fontes MR, Sampaio SV, Soares AM. Molecular approaches for structural characterization of Bothrops L-amino acid oxidases with antiprotozoal activity: cDNA cloning, comparative sequence analysis, and molecular modeling. Biochem Biophys Res Commun. 2007 Apr 6;355(2):302-6. doi:, 10.1016/j.bbrc.2006.12.217. Epub 2007 Jan 10. PMID:17292326 doi:http://dx.doi.org/10.1016/j.bbrc.2006.12.217
- ↑ Ullah A, Souza TA, Abrego JR, Betzel C, Murakami MT, Arni RK. Structural insights into selectivity and cofactor binding in snake venom l-amino acid oxidases. Biochem Biophys Res Commun. 2012 Apr 3. PMID:22490662 doi:10.1016/j.bbrc.2012.03.129
- ↑ Ullah A, Souza TA, Abrego JR, Betzel C, Murakami MT, Arni RK. Structural insights into selectivity and cofactor binding in snake venom l-amino acid oxidases. Biochem Biophys Res Commun. 2012 Apr 3. PMID:22490662 doi:10.1016/j.bbrc.2012.03.129
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