2liu
From Proteopedia
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==NMR structure of holo-ACPI domain from CurA module from Lyngbya majuscula== | ==NMR structure of holo-ACPI domain from CurA module from Lyngbya majuscula== | ||
- | <StructureSection load='2liu' size='340' side='right' caption='[[2liu | + | <StructureSection load='2liu' size='340' side='right'caption='[[2liu]]' scene=''> |
== Structural highlights == | == Structural highlights == | ||
- | [[2liu]] is a 1 chain structure with sequence from [ | + | <table><tr><td colspan='2'>[[2liu]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Lyngbya_majuscula Lyngbya majuscula]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2LIU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2LIU FirstGlance]. <br> |
- | <b> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</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=2liu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2liu OCA], [https://pdbe.org/2liu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2liu RCSB], [https://www.ebi.ac.uk/pdbsum/2liu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2liu ProSAT]</span></td></tr> |
- | <b>Resources:</b> <span class='plainlinks'>[ | + | </table> |
+ | == Function == | ||
+ | [https://www.uniprot.org/uniprot/Q6DNF2_9CYAN Q6DNF2_9CYAN] | ||
+ | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
Polyketide synthases (PKS) and non-ribosomal peptide synthetases (NRPS) are large multidomain proteins present in microorganisms that produce bioactive compounds. Curacin A is such a bioactive compound with potent anti-proliferative activity. During its biosynthesis the growing substrate is bound covalently to an acyl carrier protein (ACP) that is able to access catalytic sites of neighboring domains for chain elongation and modification. While ACP domains usually occur as monomers, the curacin A cluster codes for a triplet ACP(ACP<sub>I</sub>-ACP<sub>II</sub>-ACP<sub>III</sub>) within the CurA PKS module. We have determined the structure of the isolated holo ACP<sub>I</sub> and show that the ACPs are independent of each other within this tridomain system. In addition, we have determined the structure of the 3-hydroxyl-3-methylglutaryl-loaded holo-ACP<sub>I</sub>, which is the substrate for the unique halogenase (Hal) domain embedded within the CurA module. We have identified the interaction surface of both proteins using mutagenesis and MALDI-based identification of product formation. Amino acids affecting product formation are located on helices II and III of ACP<sub>I</sub> and form a contiguous surface. Since the CurA Hal accepts substrate only when presented by one of the ACPs within the ACP<sub>I</sub>-ACP<sub>II</sub>-ACP<sub>III</sub> tridomain, our data provide insight into the specificity of the chlorination reaction. | Polyketide synthases (PKS) and non-ribosomal peptide synthetases (NRPS) are large multidomain proteins present in microorganisms that produce bioactive compounds. Curacin A is such a bioactive compound with potent anti-proliferative activity. During its biosynthesis the growing substrate is bound covalently to an acyl carrier protein (ACP) that is able to access catalytic sites of neighboring domains for chain elongation and modification. While ACP domains usually occur as monomers, the curacin A cluster codes for a triplet ACP(ACP<sub>I</sub>-ACP<sub>II</sub>-ACP<sub>III</sub>) within the CurA PKS module. We have determined the structure of the isolated holo ACP<sub>I</sub> and show that the ACPs are independent of each other within this tridomain system. In addition, we have determined the structure of the 3-hydroxyl-3-methylglutaryl-loaded holo-ACP<sub>I</sub>, which is the substrate for the unique halogenase (Hal) domain embedded within the CurA module. We have identified the interaction surface of both proteins using mutagenesis and MALDI-based identification of product formation. Amino acids affecting product formation are located on helices II and III of ACP<sub>I</sub> and form a contiguous surface. Since the CurA Hal accepts substrate only when presented by one of the ACPs within the ACP<sub>I</sub>-ACP<sub>II</sub>-ACP<sub>III</sub> tridomain, our data provide insight into the specificity of the chlorination reaction. | ||
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Characterization of molecular interactions between ACP and halogenase domains in the curacin A polyketide synthase.,Busche AE, Gottstein D, Hein C, Ripin N, Pader I, Tufar P, Eisman EB, Gu L, Walsh CT, Loehr F, Sherman DH, Guntert P, Dotsch V ACS Chem Biol. 2011 Nov 21. PMID:22103656<ref>PMID:22103656</ref> | Characterization of molecular interactions between ACP and halogenase domains in the curacin A polyketide synthase.,Busche AE, Gottstein D, Hein C, Ripin N, Pader I, Tufar P, Eisman EB, Gu L, Walsh CT, Loehr F, Sherman DH, Guntert P, Dotsch V ACS Chem Biol. 2011 Nov 21. PMID:22103656<ref>PMID:22103656</ref> | ||
- | From | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
+ | </div> | ||
+ | <div class="pdbe-citations 2liu" style="background-color:#fffaf0;"></div> | ||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
+ | [[Category: Large Structures]] | ||
[[Category: Lyngbya majuscula]] | [[Category: Lyngbya majuscula]] | ||
- | [[Category: Busche | + | [[Category: Busche AE]] |
- | [[Category: Dotsch | + | [[Category: Dotsch V]] |
- | [[Category: Eisman | + | [[Category: Eisman EB]] |
- | [[Category: Gottstein | + | [[Category: Gottstein D]] |
- | [[Category: Gu | + | [[Category: Gu L]] |
- | [[Category: Guntert | + | [[Category: Guntert P]] |
- | [[Category: Hein | + | [[Category: Hein C]] |
- | [[Category: Loehr | + | [[Category: Loehr F]] |
- | [[Category: Pader | + | [[Category: Pader I]] |
- | [[Category: Ripin | + | [[Category: Ripin N]] |
- | [[Category: Sherman | + | [[Category: Sherman DH]] |
- | [[Category: Tufar | + | [[Category: Tufar P]] |
- | [[Category: Walsh | + | [[Category: Walsh CT]] |
- | + | ||
- | + |
Current revision
NMR structure of holo-ACPI domain from CurA module from Lyngbya majuscula
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Categories: Large Structures | Lyngbya majuscula | Busche AE | Dotsch V | Eisman EB | Gottstein D | Gu L | Guntert P | Hein C | Loehr F | Pader I | Ripin N | Sherman DH | Tufar P | Walsh CT