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| | ==Native anSMEcpe with bound AdoMet and Kp18Cys peptide== | | ==Native anSMEcpe with bound AdoMet and Kp18Cys peptide== |
| | <StructureSection load='4k38' size='340' side='right' caption='[[4k38]], [[Resolution|resolution]] 1.83Å' scene=''> | | <StructureSection load='4k38' size='340' side='right' caption='[[4k38]], [[Resolution|resolution]] 1.83Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4k38]] is a 4 chain structure with sequence from [http://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=4K38 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4K38 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4k38]] is a 4 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=4K38 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4K38 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"><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]], [[4k37|4k37]], [[4k39|4k39]]</td></tr> | | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4k36|4k36]], [[4k37|4k37]], [[4k39|4k39]]</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 Clostridium perfringens ATCC 13124])</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> |
| - | <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=4k38 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4k38 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4k38 RCSB], [http://www.ebi.ac.uk/pdbsum/4k38 PDBsum]</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=4k38 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4k38 OCA], [http://pdbe.org/4k38 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4k38 RCSB], [http://www.ebi.ac.uk/pdbsum/4k38 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4k38 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
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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 4k38" style="background-color:#fffaf0;"></div> |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Clostridium perfringens atcc 13124]] | + | [[Category: Clop1]] |
| | [[Category: Drennan, C L]] | | [[Category: Drennan, C L]] |
| | [[Category: Goldman, P J]] | | [[Category: Goldman, P J]] |
| | [[Category: Adomet radical fold]] | | [[Category: Adomet radical fold]] |
| | [[Category: Oxidoreductase]] | | [[Category: Oxidoreductase]] |
| Structural highlights
4k38 is a 4 chain structure with sequence from Clop1. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | , , , |
| Related: | 4k36, 4k37, 4k39 |
| Gene: | CPF_0616 (CLOP1) |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
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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