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| | ==Native anSMEcpe with bound AdoMet== | | ==Native anSMEcpe with bound AdoMet== |
| - | <StructureSection load='4k37' size='340' side='right' caption='[[4k37]], [[Resolution|resolution]] 1.62Å' scene=''> | + | <StructureSection load='4k37' size='340' side='right'caption='[[4k37]], [[Resolution|resolution]] 1.62Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4k37]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Clop1 Clop1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4K37 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4K37 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4k37]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Clostridium_perfringens_ATCC_13124 Clostridium perfringens ATCC 13124]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4K37 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4K37 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SAM:S-ADENOSYLMETHIONINE'>SAM</scene>, <scene name='pdbligand=SF4:IRON/SULFUR+CLUSTER'>SF4</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SAM:S-ADENOSYLMETHIONINE'>SAM</scene>, <scene name='pdbligand=SF4:IRON/SULFUR+CLUSTER'>SF4</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4k36|4k36]], [[4k38|4k38]], [[4k39|4k39]]</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=4k37 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4k37 OCA], [https://pdbe.org/4k37 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4k37 RCSB], [https://www.ebi.ac.uk/pdbsum/4k37 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4k37 ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CPF_0616 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=195103 CLOP1])</td></tr>
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| - | <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=4k37 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4k37 OCA], [http://pdbe.org/4k37 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4k37 RCSB], [http://www.ebi.ac.uk/pdbsum/4k37 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4k37 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/ANSME_CLOP1 ANSME_CLOP1]] Involved in 'Cys-type' sulfatase maturation under anaerobic conditions. Catalyzes the post-translational modification of cysteine ('Cys-51' in the arylsulfatase CPF_0221) into 3-oxoalanine (also known as C(alpha)-formylglycine (FGly)), by a free radical chemical mechanism initiated via the reductive cleavage of S-adenosyl-L-methionine (SAM). Is also able to oxidize a serine residue in a synthetic substrate to FGly in vitro, and in a serine variant of a Cys-type sulfatase in vivo, but this activity is not physiological.<ref>PMID:16766528</ref> <ref>PMID:17335281</ref> <ref>PMID:18408004</ref> | + | [https://www.uniprot.org/uniprot/ANSME_CLOP1 ANSME_CLOP1] Involved in 'Cys-type' sulfatase maturation under anaerobic conditions. Catalyzes the post-translational modification of cysteine ('Cys-51' in the arylsulfatase CPF_0221) into 3-oxoalanine (also known as C(alpha)-formylglycine (FGly)), by a free radical chemical mechanism initiated via the reductive cleavage of S-adenosyl-L-methionine (SAM). Is also able to oxidize a serine residue in a synthetic substrate to FGly in vitro, and in a serine variant of a Cys-type sulfatase in vivo, but this activity is not physiological.<ref>PMID:16766528</ref> <ref>PMID:17335281</ref> <ref>PMID:18408004</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: Clop1]] | + | [[Category: Clostridium perfringens ATCC 13124]] |
| - | [[Category: Drennan, C L]] | + | [[Category: Large Structures]] |
| - | [[Category: Goldman, P J]] | + | [[Category: Drennan CL]] |
| - | [[Category: Adomet radical fold]] | + | [[Category: Goldman PJ]] |
| - | [[Category: Oxidoreductase]]
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| Structural highlights
Function
ANSME_CLOP1 Involved in 'Cys-type' sulfatase maturation under anaerobic conditions. Catalyzes the post-translational modification of cysteine ('Cys-51' in the arylsulfatase CPF_0221) into 3-oxoalanine (also known as C(alpha)-formylglycine (FGly)), by a free radical chemical mechanism initiated via the reductive cleavage of S-adenosyl-L-methionine (SAM). Is also able to oxidize a serine residue in a synthetic substrate to FGly in vitro, and in a serine variant of a Cys-type sulfatase in vivo, but this activity is not physiological.[1] [2] [3]
Publication Abstract from PubMed
Arylsulfatases require a maturating enzyme to perform a co- or posttranslational modification to form a catalytically essential formylglycine (FGly) residue. In organisms that live aerobically, molecular oxygen is used enzymatically to oxidize cysteine to FGly. Under anaerobic conditions, S-adenosylmethionine (AdoMet) radical chemistry is used. Here we present the structures of an anaerobic sulfatase maturating enzyme (anSME), both with and without peptidyl-substrates, at 1.6-1.8 A resolution. We find that anSMEs differ from their aerobic counterparts in using backbone-based hydrogen-bonding patterns to interact with their peptidyl-substrates, leading to decreased sequence specificity. These anSME structures from Clostridium perfringens are also the first of an AdoMet radical enzyme that performs dehydrogenase chemistry. Together with accompanying mutagenesis data, a mechanistic proposal is put forth for how AdoMet radical chemistry is coopted to perform a dehydrogenation reaction. In the oxidation of cysteine or serine to FGly by anSME, we identify D277 and an auxiliary [4Fe-4S] cluster as the likely acceptor of the final proton and electron, respectively. D277 and both auxiliary clusters are housed in a cysteine-rich C-terminal domain, termed SPASM domain, that contains homology to approximately 1,400 other unique AdoMet radical enzymes proposed to use [4Fe-4S] clusters to ligate peptidyl-substrates for subsequent modification. In contrast to this proposal, we find that neither auxiliary cluster in anSME bind substrate, and both are fully ligated by cysteine residues. Instead, our structural data suggest that the placement of these auxiliary clusters creates a conduit for electrons to travel from the buried substrate to the protein surface.
X-ray structure of an AdoMet radical activase reveals an anaerobic solution for formylglycine posttranslational modification.,Goldman PJ, Grove TL, Sites LA, McLaughlin MI, Booker SJ, Drennan CL Proc Natl Acad Sci U S A. 2013 May 21;110(21):8519-24. doi:, 10.1073/pnas.1302417110. Epub 2013 May 6. PMID:23650368[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Berteau O, Guillot A, Benjdia A, Rabot S. A new type of bacterial sulfatase reveals a novel maturation pathway in prokaryotes. J Biol Chem. 2006 Aug 11;281(32):22464-70. Epub 2006 Jun 9. PMID:16766528 doi:M602504200
- ↑ Benjdia A, Leprince J, Guillot A, Vaudry H, Rabot S, Berteau O. Anaerobic sulfatase-maturating enzymes: radical SAM enzymes able to catalyze in vitro sulfatase post-translational modification. J Am Chem Soc. 2007 Mar 28;129(12):3462-3. Epub 2007 Mar 3. PMID:17335281 doi:10.1021/ja067175e
- ↑ Benjdia A, Subramanian S, Leprince J, Vaudry H, Johnson MK, Berteau O. Anaerobic sulfatase-maturating enzymes, first dual substrate radical S-adenosylmethionine enzymes. J Biol Chem. 2008 Jun 27;283(26):17815-26. doi: 10.1074/jbc.M710074200. Epub 2008, Apr 11. PMID:18408004 doi:10.1074/jbc.M710074200
- ↑ Goldman PJ, Grove TL, Sites LA, McLaughlin MI, Booker SJ, Drennan CL. X-ray structure of an AdoMet radical activase reveals an anaerobic solution for formylglycine posttranslational modification. Proc Natl Acad Sci U S A. 2013 May 21;110(21):8519-24. doi:, 10.1073/pnas.1302417110. Epub 2013 May 6. PMID:23650368 doi:10.1073/pnas.1302417110
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