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| | ==Structure of futalosine hydrolase mutant of Helicobacter pylori strain 26695== | | ==Structure of futalosine hydrolase mutant of Helicobacter pylori strain 26695== |
| - | <StructureSection load='4bn0' size='340' side='right' caption='[[4bn0]], [[Resolution|resolution]] 2.11Å' scene=''> | + | <StructureSection load='4bn0' size='340' side='right'caption='[[4bn0]], [[Resolution|resolution]] 2.11Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4bn0]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Campylobacter_pylori Campylobacter pylori]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4BN0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4BN0 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4bn0]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Helicobacter_pylori_26695 Helicobacter pylori 26695]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4BN0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4BN0 FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4bmx|4bmx]], [[4bmy|4bmy]], [[4bmz|4bmz]]</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]] 2.11Å</td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Adenosylhomocysteine_nucleosidase Adenosylhomocysteine nucleosidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.2.9 3.2.2.9] </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=4bn0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4bn0 OCA], [https://pdbe.org/4bn0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4bn0 RCSB], [https://www.ebi.ac.uk/pdbsum/4bn0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4bn0 ProSAT]</span></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=4bn0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4bn0 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4bn0 RCSB], [http://www.ebi.ac.uk/pdbsum/4bn0 PDBsum]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/MTNN_HELPY MTNN_HELPY]] Responsible for cleavage of the glycosidic bond in both 5'-methylthioadenosine (MTA) and S-adenosylhomocysteine (SAH) (By similarity). | + | [https://www.uniprot.org/uniprot/MQMTN_HELPY MQMTN_HELPY] Catalyzes the direct conversion of aminodeoxyfutalosine (AFL) into dehypoxanthine futalosine (DHFL) and adenine via the hydrolysis of the N-glycosidic bond; this reaction seems to represent an essential step in the menaquinone biosynthesis pathway in Helicobacter species. Can also probably catalyzes the hydrolysis of 5'-methylthioadenosine (MTA) and S-adenosylhomocysteine (SAH) to adenine and the corresponding thioribose, 5'-methylthioribose and S-ribosylhomocysteine, respectively. These other activities highlight the tremendous versatility of the enzyme, which also plays key roles in S-adenosylmethionine recycling and in the biosynthesis of the quorum-sensing molecule autoinducer-2. Does not act on futalosine (FL) as substrate.<ref>PMID:21098241</ref> <ref>PMID:24083939</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | </div> | | </div> |
| | + | <div class="pdbe-citations 4bn0" style="background-color:#fffaf0;"></div> |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Adenosylhomocysteine nucleosidase]] | + | [[Category: Helicobacter pylori 26695]] |
| - | [[Category: Campylobacter pylori]] | + | [[Category: Large Structures]] |
| - | [[Category: Davies, G J]] | + | [[Category: Davies GJ]] |
| - | [[Category: Kim, R Q]] | + | [[Category: Kim RQ]] |
| - | [[Category: Offen, W A]] | + | [[Category: Offen WA]] |
| - | [[Category: Stubbs, K A]] | + | [[Category: Stubbs KA]] |
| - | [[Category: Hydrolase]]
| + | |
| Structural highlights
Function
MQMTN_HELPY Catalyzes the direct conversion of aminodeoxyfutalosine (AFL) into dehypoxanthine futalosine (DHFL) and adenine via the hydrolysis of the N-glycosidic bond; this reaction seems to represent an essential step in the menaquinone biosynthesis pathway in Helicobacter species. Can also probably catalyzes the hydrolysis of 5'-methylthioadenosine (MTA) and S-adenosylhomocysteine (SAH) to adenine and the corresponding thioribose, 5'-methylthioribose and S-ribosylhomocysteine, respectively. These other activities highlight the tremendous versatility of the enzyme, which also plays key roles in S-adenosylmethionine recycling and in the biosynthesis of the quorum-sensing molecule autoinducer-2. Does not act on futalosine (FL) as substrate.[1] [2]
Publication Abstract from PubMed
The recently discovered futalosine pathway is a promising target for the development of new antibiotics. The enzymes involved in this pathway are crucial for the biosynthesis of the essential prokaryotic respiratory compound menaquinone, and as the pathway is limited to few bacterial species such as the gastric pathogen Helicobacter pylori it is a potential target for specific antibiotics. In this report, the crystal structure of an H. pylori methylthioadenosine nucleosidase (MTAN; an enzyme with broad specificity and activity towards 6-amino-6-deoxyfutalosine), which is involved in the second step of menaquinone biosynthesis, has been elucidated at a resolution of 1.76 A and refined with R factors of Rwork = 17% and Rfree = 21%. Activity studies on the wild type and active-site mutants show that the hydrolysis of 6-amino-6-deoxyfutalosine follows a mechanism similar to that of Escherichia coli MTAN. Further evidence for this mode of action is supplied by the crystal structures of active-site mutants. Through the use of reaction intermediates, the structures give additional evidence for the previously proposed nucleosidase mechanism. These structures and the confirmed reaction mechanism will provide a structural basis for the design of new inhibitors targeting the futalosine pathway.
Structural enzymology of Helicobacter pylori methylthioadenosine nucleosidase in the futalosine pathway.,Kim RQ, Offen WA, Davies GJ, Stubbs KA Acta Crystallogr D Biol Crystallogr. 2014 Jan;70(Pt 1):177-85. doi:, 10.1107/S1399004713026655. Epub 2013 Dec 31. PMID:24419390[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Arakawa C, Kuratsu M, Furihata K, Hiratsuka T, Itoh N, Seto H, Dairi T. Diversity of the early step of the futalosine pathway. Antimicrob Agents Chemother. 2011 Feb;55(2):913-6. PMID:21098241 doi:10.1128/AAC.01362-10
- ↑ Mahanta N, Fedoseyenko D, Dairi T, Begley TP. Menaquinone biosynthesis: formation of aminofutalosine requires a unique radical SAM enzyme. J Am Chem Soc. 2013 Oct 16;135(41):15318-21. PMID:24083939 doi:10.1021/ja408594p
- ↑ Kim RQ, Offen WA, Davies GJ, Stubbs KA. Structural enzymology of Helicobacter pylori methylthioadenosine nucleosidase in the futalosine pathway. Acta Crystallogr D Biol Crystallogr. 2014 Jan;70(Pt 1):177-85. doi:, 10.1107/S1399004713026655. Epub 2013 Dec 31. PMID:24419390 doi:http://dx.doi.org/10.1107/S1399004713026655
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