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| | ==Crystal Structure of Aclacinomycin Oxidoreductase== | | ==Crystal Structure of Aclacinomycin Oxidoreductase== |
| - | <StructureSection load='2ipi' size='340' side='right' caption='[[2ipi]], [[Resolution|resolution]] 1.65Å' scene=''> | + | <StructureSection load='2ipi' size='340' side='right'caption='[[2ipi]], [[Resolution|resolution]] 1.65Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2ipi]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/As_4.1320 As 4.1320]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2IPI OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2IPI FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2ipi]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/As_4.1320 As 4.1320]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2IPI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2IPI FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=AKY:METHYL+(2S,4R)-2-ETHYL-2,5,7-TRIHYDROXY-6,11-DIOXO-4-{[2,3,6-TRIDEOXY-4-O-{2,6-DIDEOXY-4-O-[(2S,6S)-6-METHYL-5-OXOTETRAHYDRO-2H-PYRAN-2-YL]-ALPHA-D-LYXO-HEXOPYRANOSYL}-3-(DIMETHYLAMINO)-D-RIBO-HEXOPYRANOSYL]OXY}-1,2,3,4,6,11-HEXAHYDROTETRACENE-1-CARBOXYLATE'>AKY</scene>, <scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AKY:METHYL+(2S,4R)-2-ETHYL-2,5,7-TRIHYDROXY-6,11-DIOXO-4-{[2,3,6-TRIDEOXY-4-O-{2,6-DIDEOXY-4-O-[(2S,6S)-6-METHYL-5-OXOTETRAHYDRO-2H-PYRAN-2-YL]-ALPHA-D-LYXO-HEXOPYRANOSYL}-3-(DIMETHYLAMINO)-D-RIBO-HEXOPYRANOSYL]OXY}-1,2,3,4,6,11-HEXAHYDROTETRACENE-1-CARBOXYLATE'>AKY</scene>, <scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">AknOx ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=33899 AS 4.1320])</td></tr> | + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">AknOx ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=33899 AS 4.1320])</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=2ipi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ipi OCA], [http://pdbe.org/2ipi PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2ipi RCSB], [http://www.ebi.ac.uk/pdbsum/2ipi PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2ipi ProSAT]</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=2ipi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ipi OCA], [https://pdbe.org/2ipi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2ipi RCSB], [https://www.ebi.ac.uk/pdbsum/2ipi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2ipi ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/AKNOX_STRGJ AKNOX_STRGJ]] Involved in the modification of the terminal sugar residues in the last two steps in the biosynthesis of polyketide antibiotics of the aclacinomycin group. In the first reaction, it catalyzes the oxidation of the hydroxyl group at carbon C4 of the L-rhodinose terminal sugar moiety of aclacinomycin N (AclN) to a keto group, modifying the sugar to cinerulose A and generating aclacinomycin A (AclA). In the second reaction, it catalyzes the elimination of two hydrogen atoms from cinerulose A, leading to a double bond between carbon atoms C2 and C3 and the generation of the L-aculose terminal sugar moiety of aclacinomycin Y (AclY). It can also use aclacinomycin analogs, epsilon-pyrromycinone glycosides, rhodirubins (A, B, C and E) and all triglycosides containing L-cinerulose, L-rhodinose or 2-deoxy-L-fucose as terminal sugar.<ref>PMID:12137949</ref> <ref>PMID:17395717</ref> <ref>PMID:528393</ref> | + | [[https://www.uniprot.org/uniprot/AKNOX_STRGJ AKNOX_STRGJ]] Involved in the modification of the terminal sugar residues in the last two steps in the biosynthesis of polyketide antibiotics of the aclacinomycin group. In the first reaction, it catalyzes the oxidation of the hydroxyl group at carbon C4 of the L-rhodinose terminal sugar moiety of aclacinomycin N (AclN) to a keto group, modifying the sugar to cinerulose A and generating aclacinomycin A (AclA). In the second reaction, it catalyzes the elimination of two hydrogen atoms from cinerulose A, leading to a double bond between carbon atoms C2 and C3 and the generation of the L-aculose terminal sugar moiety of aclacinomycin Y (AclY). It can also use aclacinomycin analogs, epsilon-pyrromycinone glycosides, rhodirubins (A, B, C and E) and all triglycosides containing L-cinerulose, L-rhodinose or 2-deoxy-L-fucose as terminal sugar.<ref>PMID:12137949</ref> <ref>PMID:17395717</ref> <ref>PMID:528393</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: As 4 1320]] | | [[Category: As 4 1320]] |
| | + | [[Category: Large Structures]] |
| | [[Category: Alexeev, I]] | | [[Category: Alexeev, I]] |
| | [[Category: Kursula, I]] | | [[Category: Kursula, I]] |
| Structural highlights
Function
[AKNOX_STRGJ] Involved in the modification of the terminal sugar residues in the last two steps in the biosynthesis of polyketide antibiotics of the aclacinomycin group. In the first reaction, it catalyzes the oxidation of the hydroxyl group at carbon C4 of the L-rhodinose terminal sugar moiety of aclacinomycin N (AclN) to a keto group, modifying the sugar to cinerulose A and generating aclacinomycin A (AclA). In the second reaction, it catalyzes the elimination of two hydrogen atoms from cinerulose A, leading to a double bond between carbon atoms C2 and C3 and the generation of the L-aculose terminal sugar moiety of aclacinomycin Y (AclY). It can also use aclacinomycin analogs, epsilon-pyrromycinone glycosides, rhodirubins (A, B, C and E) and all triglycosides containing L-cinerulose, L-rhodinose or 2-deoxy-L-fucose as terminal sugar.[1] [2] [3]
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
The crystal structure of aclacinomycin oxidoreductase (AknOx), a tailoring enzyme involved in the biosynthesis of the polyketide antibiotic aclacinomycin, was determined to 1.65 A resolution by multiwavelength anomalous diffraction using data from selenomethionine-substituted crystals. The crystals belong to space group P2(1), with unit-cell parameters a = 68.2, b = 264.5, c = 68.2 A, beta = 119 degrees . Analysis of the intensity statistics clearly showed the presence of pseudomerohedral twinning. The data set could also be indexed and scaled with an R(sym) of 0.072 in the orthorhombic space group C222(1) (unit-cell parameters a = 69.7, b = 117.5, c = 264.4 A), indicating the possibility of pseudomerohedral twinning along the diagonal between the monoclinic a and c directions. Refinement using this twin operator resulted in an R(free) of 24.2%. A monoclinic lattice with a = c and beta close to 120 degrees can emulate a hexagonal metric, with the possibility of a threefold twin operator along the b axis and three twin domains. Refinement assuming three-domain twinning gave a final R(free) of 26.5%. The structure of AknOx can be thus refined with comparable R(free) values using either of the twin operators separately, suggesting the possibility that crystals of AknOx contain six twin domains generated by the twofold and threefold twin operators perpendicular to each other. Both twin operators coincide with noncrystallographic symmetry axes that may promote twinning.
Structure determination by multiwavelength anomalous diffraction of aclacinomycin oxidoreductase: indications of multidomain pseudomerohedral twinning.,Sultana A, Alexeev I, Kursula I, Mantsala P, Niemi J, Schneider G Acta Crystallogr D Biol Crystallogr. 2007 Feb;63(Pt 2):149-59. Epub 2007, Jan 16. PMID:17242508[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Raty K, Kantola J, Hautala A, Hakala J, Ylihonko K, Mantsala P. Cloning and characterization of Streptomyces galilaeus aclacinomycins polyketide synthase (PKS) cluster. Gene. 2002 Jun 26;293(1-2):115-22. PMID:12137949
- ↑ Alexeev I, Sultana A, Mantsala P, Niemi J, Schneider G. Aclacinomycin oxidoreductase (AknOx) from the biosynthetic pathway of the antibiotic aclacinomycin is an unusual flavoenzyme with a dual active site. Proc Natl Acad Sci U S A. 2007 Apr 10;104(15):6170-5. Epub 2007 Mar 29. PMID:17395717 doi:10.1073/pnas.0700579104
- ↑ Yoshimoto A, Ogasawara T, Kitamura I, Oki T, Inui T, Takeuchi T, Umezawa H. Enzymatic conversion of aclacinomycin A to Y by a specific oxidoreductase in Streptomyces. J Antibiot (Tokyo). 1979 May;32(5):472-81. PMID:528393
- ↑ Sultana A, Alexeev I, Kursula I, Mantsala P, Niemi J, Schneider G. Structure determination by multiwavelength anomalous diffraction of aclacinomycin oxidoreductase: indications of multidomain pseudomerohedral twinning. Acta Crystallogr D Biol Crystallogr. 2007 Feb;63(Pt 2):149-59. Epub 2007, Jan 16. PMID:17242508 doi:http://dx.doi.org/10.1107/S0907444906044271
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