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| | ==Helicobacter pylori MTAN complexed with S-ribosylhomocysteine and adenine== | | ==Helicobacter pylori MTAN complexed with S-ribosylhomocysteine and adenine== |
| - | <StructureSection load='4ojt' size='340' side='right' caption='[[4ojt]], [[Resolution|resolution]] 1.50Å' scene=''> | + | <StructureSection load='4ojt' size='340' side='right'caption='[[4ojt]], [[Resolution|resolution]] 1.50Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4ojt]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Campylobacter_pylori_j99 Campylobacter pylori j99]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4OJT OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4OJT FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4ojt]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Helicobacter_pylori_J99 Helicobacter pylori J99]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4OJT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4OJT FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=2WP:(2S)-2-AMINO-4-({[(2S,3S,4R,5S)-3,4,5-TRIHYDROXYTETRAHYDROFURAN-2-YL]METHYL}SULFANYL)BUTANOIC+ACID'>2WP</scene>, <scene name='pdbligand=ADE:ADENINE'>ADE</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2WP:(2S)-2-AMINO-4-({[(2S,3S,4R,5S)-3,4,5-TRIHYDROXYTETRAHYDROFURAN-2-YL]METHYL}SULFANYL)BUTANOIC+ACID'>2WP</scene>, <scene name='pdbligand=ADE:ADENINE'>ADE</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3nm4|3nm4]], [[3nm5|3nm5]], [[3nm6|3nm6]]</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=4ojt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ojt OCA], [https://pdbe.org/4ojt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ojt RCSB], [https://www.ebi.ac.uk/pdbsum/4ojt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ojt ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">jhp_0082, mtn, mtnN, pfs ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=85963 Campylobacter pylori J99])</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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ojt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ojt OCA], [http://pdbe.org/4ojt PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4ojt RCSB], [http://www.ebi.ac.uk/pdbsum/4ojt PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4ojt ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/MTNN_HELPJ MTNN_HELPJ]] Responsible for cleavage of the glycosidic bond in both 5'-methylthioadenosine (MTA) and S-adenosylhomocysteine (SAH) (By similarity). | + | [https://www.uniprot.org/uniprot/MQMTN_HELPJ MQMTN_HELPJ] 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. Also catalyzes the hydrolysis of 5'-methylthioadenosine (MTA) to adenine and 5'-methylthioribose. Can also probably use S-adenosylhomocysteine (SAH) as substrate, leading to adenine and S-ribosylhomocysteine. 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.<ref>PMID:20954236</ref> <ref>PMID:22891633</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Adenosylhomocysteine nucleosidase]] | + | [[Category: Helicobacter pylori J99]] |
| - | [[Category: Campylobacter pylori j99]] | + | [[Category: Large Structures]] |
| - | [[Category: Mishra, V]] | + | [[Category: Mishra V]] |
| - | [[Category: Ronning, D R]] | + | [[Category: Ronning DR]] |
| - | [[Category: Homodimer]]
| + | |
| - | [[Category: Hydrolase]]
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| Structural highlights
Function
MQMTN_HELPJ 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. Also catalyzes the hydrolysis of 5'-methylthioadenosine (MTA) to adenine and 5'-methylthioribose. Can also probably use S-adenosylhomocysteine (SAH) as substrate, leading to adenine and S-ribosylhomocysteine. 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.[1] [2]
Publication Abstract from PubMed
The bacterial 5'-methylthioadenosine/S-adenosylhomocysteine nucleosidase (MTAN) enzyme is a multifunctional enzyme that catalyzes the hydrolysis of the N-ribosidic bond of at least four different adenosine-based metabolites: S-adenosylhomocysteine (SAH), 5'-methylthioadenosine (MTA), 5'-deoxyadenosine (5'-DOA), and 6-amino-6-deoxyfutalosine. These activities place the enzyme at the hub of seven fundamental bacterial metabolic pathways: S-adenosylmethionine (SAM) utilization, polyamine biosynthesis, the purine salvage pathway, the methionine salvage pathway, the SAM radical pathways, autoinducer-2 biosynthesis, and menaquinone biosynthesis. The last pathway makes MTAN essential for Helicobacter pylori viability. Although structures of various bacterial and plant MTANs have been described, the interactions between the homocysteine moiety of SAH and the 5'-alkylthiol binding site of MTAN have never been resolved. We have determined crystal structures of an inactive mutant form of H. pylori MTAN bound to MTA and SAH to 1.63 and 1.20 A, respectively. The active form of MTAN was also crystallized in the presence of SAH, allowing the determination of the structure of a ternary enzyme-product complex resolved at 1.50 A. These structures identify interactions between the homocysteine moiety and the 5'-alkylthiol binding site of the enzyme. This information can be leveraged for the development of species-specific MTAN inhibitors that prevent the growth of H. pylori.
Crystal structures of the Helicobacter pylori MTAN enzyme reveal specific interactions between S-adenosylhomocysteine and the 5'-alkylthio binding subsite.,Mishra V, Ronning DR Biochemistry. 2012 Dec 4;51(48):9763-72. doi: 10.1021/bi301221k. Epub 2012 Nov, 20. PMID:23148563[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Ronning DR, Iacopelli NM, Mishra V. Enzyme-ligand interactions that drive active site rearrangements in the Helicobacter pylori 5'-methylthioadenosine/S-adenosylhomocysteine nucleosidase. Protein Sci. 2010 Oct 15. PMID:20954236 doi:10.1002/pro.524
- ↑ Wang S, Haapalainen AM, Yan F, Du Q, Tyler PC, Evans GB, Rinaldo-Matthis A, Brown RL, Norris GE, Almo SC, Schramm VL. A Picomolar Transition State Analogue Inhibitor of MTAN as a Specific Antibiotic for Helicobacter pylori. Biochemistry. 2012 Sep 4;51(35):6892-4. Epub 2012 Aug 22. PMID:22891633 doi:http://dx.doi.org/10.1021/bi3009664
- ↑ Mishra V, Ronning DR. Crystal structures of the Helicobacter pylori MTAN enzyme reveal specific interactions between S-adenosylhomocysteine and the 5'-alkylthio binding subsite. Biochemistry. 2012 Dec 4;51(48):9763-72. doi: 10.1021/bi301221k. Epub 2012 Nov, 20. PMID:23148563 doi:http://dx.doi.org/10.1021/bi301221k
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