3f5h

From Proteopedia

(Difference between revisions)

Current revision

Crystal structure of fused docking domains from PikAIII and PikAIV of the pikromycin polyketide synthase

Structural highlights

3f5h is a 2 chain structure with sequence from Streptomyces venezuelae. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.75Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

PIKA4_STRVZ Involved in the biosynthesis of 12- and 14-membered ring macrolactone antibiotics such as methymycin and neomethymycin, and pikromycin and narbomycin, respectively. Component of the pikromycin PKS which catalyzes the biosynthesis of both precursors 10-deoxymethynolide (12-membered ring macrolactone) and narbonolide (14-membered ring macrolactone). Chain elongation through PikAI, PikAII and PikAIII followed by thioesterase catalyzed termination results in the production of 10-deoxymethynolide, while continued elongation through PikAIV, followed by thioesterase (TE) catalyzed cyclization results in the biosynthesis of the narbonolide. The thioesterase can use a series of diketide-N-acetylcysteamine (SNAC) thioesters, but has a strong preference for the 2-methyl-3-ketopentanoyl-SNAC over the stereoisomers of 2-methyl-3-hydroxyacyl-SNAC (PubMed:12379101, PubMed:12733905).^[1] ^[2] ^[3] ^[4] ^[5] ^[6] ^[7] PIKA3_STRVZ Involved in the biosynthesis of 12- and 14-membered ring macrolactone antibiotics such as methymycin and neomethymycin, and pikromycin and narbomycin, respectively. Component of the pikromycin PKS which catalyzes the biosynthesis of both precursors 10-deoxymethynolide (12-membered ring macrolactone) and narbonolide (14-membered ring macrolactone). Chain elongation through PikAI, PikAII and PikAIII followed by thioesterase catalyzed termination results in the production of 10-deoxymethynolide, while continued elongation through PikAIV, followed by thioesterase (TE) catalyzed cyclization results in the biosynthesis of the narbonolide.^[8] ^[9] ^[10]

Publication Abstract from PubMed

Bacterial type I polyketide synthases (PKSs) assemble structurally diverse natural products of significant clinical value from simple metabolic building blocks. The synthesis of these compounds occurs in a processive fashion along a large multiprotein complex. Transfer of the acyl intermediate across interpolypeptide junctions is mediated, at least in large part, by N- and C-terminal docking domains. We report here a comprehensive analysis of the binding affinity and selectivity for the complete set of discrete docking domain pairs in the pikromycin and erythromycin PKS systems. Despite disconnection from their parent module, each cognate pair of docking domains retained exquisite binding selectivity. Further insights were obtained by X-ray crystallographic analysis of the PikAIII/PikAIV docking domain interface. This new information revealed a series of key interacting residues that enabled development of a structural model for the recently proposed H2-T2 class of polypeptides involved in PKS intermodular molecular recognition.

Structural basis for binding specificity between subclasses of modular polyketide synthase docking domains.,Buchholz TJ, Geders TW, Bartley FE 3rd, Reynolds KA, Smith JL, Sherman DH ACS Chem Biol. 2009 Jan 16;4(1):41-52. PMID:19146481^[11]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Tang L, Fu H, Betlach MC, McDaniel R. Elucidating the mechanism of chain termination switching in the picromycin/methymycin polyketide synthase. Chem Biol. 1999 Aug;6(8):553-8. doi: 10.1016/S1074-5521(99)80087-8. PMID:10421766 doi:http://dx.doi.org/10.1016/S1074-5521(99)80087-8
↑ Xue Y, Sherman DH. Alternative modular polyketide synthase expression controls macrolactone structure. Nature. 2000 Feb 3;403(6769):571-5. PMID:10676969 doi:10.1038/35000624
↑ Lu H, Tsai SC, Khosla C, Cane DE. Expression, site-directed mutagenesis, and steady state kinetic analysis of the terminal thioesterase domain of the methymycin/picromycin polyketide synthase. Biochemistry. 2002 Oct 22;41(42):12590-7. PMID:12379101 doi:10.1021/bi026006d
↑ Yin Y, Lu H, Khosla C, Cane DE. Expression and kinetic analysis of the substrate specificity of modules 5 and 6 of the picromycin/methymycin polyketide synthase. J Am Chem Soc. 2003 May 14;125(19):5671-6. PMID:12733905 doi:10.1021/ja034574q
↑ Akey DL, Kittendorf JD, Giraldes JW, Fecik RA, Sherman DH, Smith JL. Structural basis for macrolactonization by the pikromycin thioesterase. Nat Chem Biol. 2006 Oct;2(10):537-42. Epub 2006 Sep 10. PMID:16969372 doi:10.1038/nchembio824
↑ Kittendorf JD, Beck BJ, Buchholz TJ, Seufert W, Sherman DH. Interrogating the molecular basis for multiple macrolactone ring formation by the pikromycin polyketide synthase. Chem Biol. 2007 Aug;14(8):944-54. PMID:17719493 doi:10.1016/j.chembiol.2007.07.013
↑ Kittendorf JD, Sherman DH. The methymycin/pikromycin pathway: a model for metabolic diversity in natural product biosynthesis. Bioorg Med Chem. 2009 Mar 15;17(6):2137-46. doi: 10.1016/j.bmc.2008.10.082. Epub , 2008 Nov 5. PMID:19027305 doi:http://dx.doi.org/10.1016/j.bmc.2008.10.082
↑ Tang L, Fu H, Betlach MC, McDaniel R. Elucidating the mechanism of chain termination switching in the picromycin/methymycin polyketide synthase. Chem Biol. 1999 Aug;6(8):553-8. doi: 10.1016/S1074-5521(99)80087-8. PMID:10421766 doi:http://dx.doi.org/10.1016/S1074-5521(99)80087-8
↑ Whicher JR, Dutta S, Hansen DA, Hale WA, Chemler JA, Dosey AM, Narayan AR, Håkansson K, Sherman DH, Smith JL, Skiniotis G. Structural rearrangements of a polyketide synthase module during its catalytic cycle. Nature. 2014 Jun 26;510(7506):560-4. PMID:24965656 doi:10.1038/nature13409
↑ Kittendorf JD, Sherman DH. The methymycin/pikromycin pathway: a model for metabolic diversity in natural product biosynthesis. Bioorg Med Chem. 2009 Mar 15;17(6):2137-46. doi: 10.1016/j.bmc.2008.10.082. Epub , 2008 Nov 5. PMID:19027305 doi:http://dx.doi.org/10.1016/j.bmc.2008.10.082
↑ Buchholz TJ, Geders TW, Bartley FE 3rd, Reynolds KA, Smith JL, Sherman DH. Structural basis for binding specificity between subclasses of modular polyketide synthase docking domains. ACS Chem Biol. 2009 Jan 16;4(1):41-52. PMID:19146481 doi:10.1021/cb8002607

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://proteopedia.org/wiki/index.php/3f5h"

@@ Line 3: / Line 3: @@
 <StructureSection load='3f5h' size='340' side='right'caption='[[3f5h]], [[Resolution|resolution]] 1.75&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3f5h]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/As_4.1526 As 4.1526]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3F5H OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3F5H FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3f5h]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Streptomyces_venezuelae Streptomyces venezuelae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3F5H OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3F5H FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NA:SODIUM+ION'>NA</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]] 1.75&#8491;</td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1pzr|1pzr]]</div></td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">pIKAIII, pIKAIV ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=54571 AS 4.1526])</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=3f5h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3f5h OCA], [https://pdbe.org/3f5h PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3f5h RCSB], [https://www.ebi.ac.uk/pdbsum/3f5h PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3f5h ProSAT]</span></td></tr>
 </table>
+== Function ==
+[https://www.uniprot.org/uniprot/PIKA4_STRVZ PIKA4_STRVZ] Involved in the biosynthesis of 12- and 14-membered ring macrolactone antibiotics such as methymycin and neomethymycin, and pikromycin and narbomycin, respectively. Component of the pikromycin PKS which catalyzes the biosynthesis of both precursors 10-deoxymethynolide (12-membered ring macrolactone) and narbonolide (14-membered ring macrolactone). Chain elongation through PikAI, PikAII and PikAIII followed by thioesterase catalyzed termination results in the production of 10-deoxymethynolide, while continued elongation through PikAIV, followed by thioesterase (TE) catalyzed cyclization results in the biosynthesis of the narbonolide. The thioesterase can use a series of diketide-N-acetylcysteamine (SNAC) thioesters, but has a strong preference for the 2-methyl-3-ketopentanoyl-SNAC over the stereoisomers of 2-methyl-3-hydroxyacyl-SNAC (PubMed:12379101, PubMed:12733905).<ref>PMID:10421766</ref> <ref>PMID:10676969</ref> <ref>PMID:12379101</ref> <ref>PMID:12733905</ref> <ref>PMID:16969372</ref> <ref>PMID:17719493</ref> <ref>PMID:19027305</ref> [https://www.uniprot.org/uniprot/PIKA3_STRVZ PIKA3_STRVZ] Involved in the biosynthesis of 12- and 14-membered ring macrolactone antibiotics such as methymycin and neomethymycin, and pikromycin and narbomycin, respectively. Component of the pikromycin PKS which catalyzes the biosynthesis of both precursors 10-deoxymethynolide (12-membered ring macrolactone) and narbonolide (14-membered ring macrolactone). Chain elongation through PikAI, PikAII and PikAIII followed by thioesterase catalyzed termination results in the production of 10-deoxymethynolide, while continued elongation through PikAIV, followed by thioesterase (TE) catalyzed cyclization results in the biosynthesis of the narbonolide.<ref>PMID:10421766</ref> <ref>PMID:24965656</ref> <ref>PMID:19027305</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 22: / Line 23: @@
 __TOC__
 </StructureSection>
-[[Category: As 4 1526]]
 [[Category: Large Structures]]
-[[Category: Bartley, F E]]
+[[Category: Streptomyces venezuelae]]
-[[Category: Buchholz, T J]]
+[[Category: Bartley FE]]
-[[Category: Geders, T W]]
+[[Category: Buchholz TJ]]
-[[Category: Reynolds, K A]]
+[[Category: Geders TW]]
-[[Category: Sherman, D H]]
+[[Category: Reynolds KA]]
-[[Category: Smith, J L]]
+[[Category: Sherman DH]]
-[[Category: Docking domain]]
+[[Category: Smith JL]]
-[[Category: H2-t2]]
-[[Category: Pikromycin]]
-[[Category: Polyketide synthase]]
-[[Category: Protein binding]]

3f5h

From Proteopedia

Current revision

Crystal structure of fused docking domains from PikAIII and PikAIV of the pikromycin polyketide synthase

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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