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==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]] 1.90&Aring;' scene=''>
<StructureSection load='4ffs' size='340' side='right'caption='[[4ffs]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[4ffs]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Helicobacter_pylori Helicobacter pylori]. 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><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><br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.9&#8491;</td></tr>
<tr><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=210 Helicobacter pylori])</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><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=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><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://www.rcsb.org/pdb/explore.do?structureId=4ffs RCSB], [http://www.ebi.ac.uk/pdbsum/4ffs PDBsum]</span></td></tr>
</table>
<table>
== Function ==
<div style="background-color:#fffaf0;">
[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>  
== 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 &lt;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<ref>PMID:22891633</ref>
 
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Adenosylhomocysteine nucleosidase]]
[[Category: Helicobacter pylori J99]]
[[Category: Helicobacter pylori]]
[[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]]

Latest revision as of 14:16, 1 March 2024

Crystal structure of 5'-methylthioadenosine/S-adenosylhomocysteine nucleosidase from Helicobacter pylori with butyl-thio-DADMe-Immucillin-ACrystal structure of 5'-methylthioadenosine/S-adenosylhomocysteine nucleosidase from Helicobacter pylori with butyl-thio-DADMe-Immucillin-A

Structural highlights

4ffs is a 1 chain structure with sequence from Helicobacter pylori J99. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 1.9Å
Ligands:,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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]

References

  1. ↑ 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
  2. ↑ 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

4ffs, resolution 1.90Å

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