|
|
| Line 1: |
Line 1: |
| | | | |
| | ==Crystal structure of 5'-methylthioadenosine/S-adenosylhomocysteine nucleosidase from Helicobacter pylori with butyl-thio-DADMe-Immucillin-A== | | ==Crystal structure of 5'-methylthioadenosine/S-adenosylhomocysteine nucleosidase from Helicobacter pylori with butyl-thio-DADMe-Immucillin-A== |
| - | <StructureSection load='4ffs' size='340' side='right' caption='[[4ffs]], [[Resolution|resolution]] 1.90Å' scene=''> | + | <StructureSection load='4ffs' size='340' side='right'caption='[[4ffs]], [[Resolution|resolution]] 1.90Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4ffs]] 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=4FFS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4FFS FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4ffs]] 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=4FFS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4FFS FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BIG:(3R,4S)-1-[(4-AMINO-5H-PYRROLO[3,2-D]PYRIMIDIN-7-YL)METHYL]-4-[(BUTYLSULFANYL)METHYL]PYRROLIDIN-3-OL'>BIG</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BIG:(3R,4S)-1-[(4-AMINO-5H-PYRROLO[3,2-D]PYRIMIDIN-7-YL)METHYL]-4-[(BUTYLSULFANYL)METHYL]PYRROLIDIN-3-OL'>BIG</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene></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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4ffs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ffs OCA], [https://pdbe.org/4ffs PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ffs RCSB], [https://www.ebi.ac.uk/pdbsum/4ffs PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ffs ProSAT]</span></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=4ffs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ffs OCA], [http://pdbe.org/4ffs PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4ffs RCSB], [http://www.ebi.ac.uk/pdbsum/4ffs PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4ffs 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 == |
| Line 24: |
Line 22: |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Adenosylhomocysteine nucleosidase]] | + | [[Category: Helicobacter pylori J99]] |
| - | [[Category: Campylobacter pylori j99]] | + | [[Category: Large Structures]] |
| - | [[Category: Almo, S C]] | + | [[Category: Almo SC]] |
| - | [[Category: Brown, R L]] | + | [[Category: Brown RL]] |
| - | [[Category: Haapalainen, A M]] | + | [[Category: Haapalainen AM]] |
| - | [[Category: Norris, G E]] | + | [[Category: Norris GE]] |
| - | [[Category: Rinaldo-Matthis, A]] | + | [[Category: Rinaldo-Matthis A]] |
| - | [[Category: Schramm, V L]] | + | [[Category: Schramm VL]] |
| - | [[Category: 5'-methylthioadenosine/s-adenosylhomocysteine nucleosidase]]
| + | |
| - | [[Category: Acting on glycosyl bond]]
| + | |
| - | [[Category: Adenosylhomocysteine nucleosidase activity]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Hydrolase activity]]
| + | |
| - | [[Category: L-methionine biosynthetic process from s-adenosylmethionine]]
| + | |
| - | [[Category: L-methionine salvage from methylthioadenosine]]
| + | |
| - | [[Category: Methylthioadenosine nucleosidase activity]]
| + | |
| 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
Campylobacter and Helicobacter species express a 6-amino-6-deoxyfutalosine N-ribosylhydrolase (HpMTAN) proposed to function in menaquinone synthesis. BuT-DADMe-ImmA is a 36 pM transition state analogue of HpMTAN, and the crystal structure of the enzyme-inhibitor complex reveals the mechanism of inhibition. BuT-DADMe-ImmA has a MIC(90) value of <8 ng/mL for Helicobacter pylori growth but does not cause growth arrest in other common clinical pathogens, thus demonstrating potential as an H. pylori-specific antibiotic.
A Picomolar Transition State Analogue Inhibitor of MTAN as a Specific Antibiotic for Helicobacter pylori.,Wang S, Haapalainen AM, Yan F, Du Q, Tyler PC, Evans GB, Rinaldo-Matthis A, Brown RL, Norris GE, Almo SC, Schramm VL Biochemistry. 2012 Sep 4;51(35):6892-4. Epub 2012 Aug 22. PMID:22891633[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
- ↑ 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
|
