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| <StructureSection load='6j9d' size='340' side='right'caption='[[6j9d]], [[Resolution|resolution]] 2.90Å' scene=''> | | <StructureSection load='6j9d' size='340' side='right'caption='[[6j9d]], [[Resolution|resolution]] 2.90Å' scene=''> |
| == Structural highlights == | | == Structural highlights == |
| <table><tr><td colspan='2'>[[6j9d]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Babmr Babmr]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6J9D OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6J9D FirstGlance]. <br> | | <table><tr><td colspan='2'>[[6j9d]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Babesia_microti_strain_RI Babesia microti strain RI]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6J9D OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6J9D FirstGlance]. <br> |
| </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">BMR1_01G00020 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1133968 BABMR])</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]] 2.904Å</td></tr> |
| <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/L-lactate_dehydrogenase L-lactate dehydrogenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.27 1.1.1.27] </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=6j9d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6j9d OCA], [https://pdbe.org/6j9d PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6j9d RCSB], [https://www.ebi.ac.uk/pdbsum/6j9d PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6j9d ProSAT]</span></td></tr> |
| <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6j9d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6j9d OCA], [http://pdbe.org/6j9d PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6j9d RCSB], [http://www.ebi.ac.uk/pdbsum/6j9d PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6j9d ProSAT]</span></td></tr> | |
| </table> | | </table> |
| <div style="background-color:#fffaf0;">
| | == Function == |
| == Publication Abstract from PubMed == | | [https://www.uniprot.org/uniprot/I7J7V6_BABMR I7J7V6_BABMR] |
| The tick- and transfusion-transmitted human pathogen Babesia microti infects host erythrocytes to cause the pathologic symptoms associated with human babesiosis, an emerging disease with worldwide distribution and potentially fatal clinical outcome. Drugs currently recommended for the treatment of babesiosis are associated with a high failure rate and significant adverse events, highlighting the urgent need for more-effective and safer babesiosis therapies. Unlike other apicomplexan parasites, B. microti lacks a canonical lactate dehydrogenase (LDH) but instead expresses a unique enzyme, B. microti LDH (BmLDH), acquired through evolution by horizontal transfer from a mammalian host. Here, we report the crystal structures of BmLDH in apo state and ternary complex (enzyme-NADH-oxamate) solved at 2.79 and 1.89 A. Analysis of these structures reveals that upon binding to the coenzyme and substrate, the active pocket of BmLDH undergoes a major conformational change from an opened and disordered to a closed and stabilized state. Biochemical assays using wild-type and mutant B. microti and human LDHs identified Arg99 as a critical residue for the catalytic activity of BmLDH but not its human counterpart. Interestingly, mutation of Arg99 to Ala had no impact on the overall structure and affinity of BmLDH to NADH but dramatically altered the closure of the enzyme's active pocket. Together, these structural and biochemical data highlight significant differences between B. microti and human LDH enzymes and suggest that BmLDH could be a suitable target for the development of selective antibabesial inhibitors.-Yu, L., Shen, Z., Liu, Q., Zhan, X., Luo, X., An, X., Sun, Y., Li, M., Wang, S., Nie, Z., Ao, Y., Zhao, Y., Peng, G., Ben Mamoun, C., He, L., Zhao, J. Crystal structures of Babesia microti lactate dehydrogenase BmLDH reveal a critical role for Arg99 in catalysis.
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| Crystal structures of Babesia microti lactate dehydrogenase BmLDH reveal a critical role for Arg99 in catalysis.,Yu L, Shen Z, Liu Q, Zhan X, Luo X, An X, Sun Y, Li M, Wang S, Nie Z, Ao Y, Zhao Y, Peng G, Mamoun CB, He L, Zhao J FASEB J. 2019 Dec;33(12):13669-13682. doi: 10.1096/fj.201901259R. Epub 2019 Oct, 4. PMID:31585506<ref>PMID:31585506</ref>
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| From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| </div>
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| <div class="pdbe-citations 6j9d" style="background-color:#fffaf0;"></div>
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| ==See Also== | | ==See Also== |
| *[[Lactate dehydrogenase 3D structures|Lactate dehydrogenase 3D structures]] | | *[[Lactate dehydrogenase 3D structures|Lactate dehydrogenase 3D structures]] |
| == References ==
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| <references/>
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| __TOC__ | | __TOC__ |
| </StructureSection> | | </StructureSection> |
| [[Category: Babmr]] | | [[Category: Babesia microti strain RI]] |
| [[Category: L-lactate dehydrogenase]]
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| [[Category: Large Structures]] | | [[Category: Large Structures]] |
| [[Category: Yu, L]] | | [[Category: Yu L]] |
| [[Category: Bmldh]]
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| [[Category: Oxidoreductase]]
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