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| | ==salL with ClDA and LMet== | | ==salL with ClDA and LMet== |
| - | <StructureSection load='2q6i' size='340' side='right' caption='[[2q6i]], [[Resolution|resolution]] 2.60Å' scene=''> | + | <StructureSection load='2q6i' size='340' side='right'caption='[[2q6i]], [[Resolution|resolution]] 2.60Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2q6i]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Salto Salto]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2Q6I OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2Q6I FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2q6i]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Salinispora_tropica_CNB-440 Salinispora tropica CNB-440]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2Q6I OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2Q6I FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=5CD:5-CHLORO-5-DEOXYADENOSINE'>5CD</scene>, <scene name='pdbligand=MET:METHIONINE'>MET</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.6Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2q6k|2q6k]], [[2q6o|2q6o]], [[2q6l|2q6l]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=5CD:5-CHLORO-5-DEOXYADENOSINE'>5CD</scene>, <scene name='pdbligand=MET:METHIONINE'>MET</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">salL ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=369723 SALTO])</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=2q6i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2q6i OCA], [https://pdbe.org/2q6i PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2q6i RCSB], [https://www.ebi.ac.uk/pdbsum/2q6i PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2q6i ProSAT]</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=2q6i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2q6i OCA], [http://pdbe.org/2q6i PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2q6i RCSB], [http://www.ebi.ac.uk/pdbsum/2q6i PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2q6i ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/SALL_SALTO SALL_SALTO]] Involved in the biosynthesis of the proteosome inhibitor salinosporamide A (SalA). Catalyzes the halogenation of S-adenosyl-L-methionine (SAM) with chloride to generate 5'-chloro-5'-deoxyadenosine (5'-CIDA) and L-methionine. It can also use bromide and iodide, producing halogenated 5'-deoxyadenosine (5'-XDA) and L-methionine, however no halogenase activity is detected in the presence of fluoride.<ref>PMID:18059261</ref> | + | [https://www.uniprot.org/uniprot/SALL_SALTO SALL_SALTO] Involved in the biosynthesis of the proteosome inhibitor salinosporamide A (SalA). Catalyzes the halogenation of S-adenosyl-L-methionine (SAM) with chloride to generate 5'-chloro-5'-deoxyadenosine (5'-CIDA) and L-methionine. It can also use bromide and iodide, producing halogenated 5'-deoxyadenosine (5'-XDA) and L-methionine, however no halogenase activity is detected in the presence of fluoride.<ref>PMID:18059261</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Salto]] | + | [[Category: Large Structures]] |
| - | [[Category: Noel, J P]] | + | [[Category: Salinispora tropica CNB-440]] |
| - | [[Category: Pojer, F]] | + | [[Category: Noel JP]] |
| - | [[Category: Biosynthetic protein]] | + | [[Category: Pojer F]] |
| - | [[Category: Chlorinase]]
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| - | [[Category: Clda and l-met complex]]
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| Structural highlights
Function
SALL_SALTO Involved in the biosynthesis of the proteosome inhibitor salinosporamide A (SalA). Catalyzes the halogenation of S-adenosyl-L-methionine (SAM) with chloride to generate 5'-chloro-5'-deoxyadenosine (5'-CIDA) and L-methionine. It can also use bromide and iodide, producing halogenated 5'-deoxyadenosine (5'-XDA) and L-methionine, however no halogenase activity is detected in the presence of fluoride.[1]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Halogen atom incorporation into a scaffold of bioactive compounds often amplifies biological activity, as is the case for the anticancer agent salinosporamide A (1), a chlorinated natural product from the marine bacterium Salinispora tropica. Significant effort in understanding enzymatic chlorination shows that oxidative routes predominate to form reactive electrophilic or radical chlorine species. Here we report the genetic, biochemical and structural characterization of the chlorinase SalL, which halogenates S-adenosyl-L-methionine (2) with chloride to generate 5'-chloro-5'-deoxyadenosine (3) and L-methionine (4) in a rarely observed nucleophilic substitution strategy analogous to that of Streptomyces cattleya fluorinase. Further metabolic tailoring produces a halogenated polyketide synthase substrate specific for salinosporamide A biosynthesis. SalL also accepts bromide and iodide as substrates, but not fluoride. High-resolution crystal structures of SalL and active site mutants complexed with substrates and products support the S(N)2 nucleophilic substitution mechanism and further illuminate halide specificity in this newly discovered halogenase family.
Discovery and characterization of a marine bacterial SAM-dependent chlorinase.,Eustaquio AS, Pojer F, Noel JP, Moore BS Nat Chem Biol. 2008 Jan;4(1):69-74. Epub 2007 Dec 2. PMID:18059261[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Eustaquio AS, Pojer F, Noel JP, Moore BS. Discovery and characterization of a marine bacterial SAM-dependent chlorinase. Nat Chem Biol. 2008 Jan;4(1):69-74. Epub 2007 Dec 2. PMID:18059261 doi:http://dx.doi.org/10.1038/nchembio.2007.56
- ↑ Eustaquio AS, Pojer F, Noel JP, Moore BS. Discovery and characterization of a marine bacterial SAM-dependent chlorinase. Nat Chem Biol. 2008 Jan;4(1):69-74. Epub 2007 Dec 2. PMID:18059261 doi:http://dx.doi.org/10.1038/nchembio.2007.56
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