2LIU

NMR structure of holo-ACPI domain from CurA module from Lyngbya majuscula

Summary for 2LIU

• Entry DOI: 10.2210/pdb2liu/pdb
• Related: 2LIW
• NMR Information: BMRB: 17906
• Descriptor: CurA (1 entity in total)
• Functional Keywords: holo state, transferase
• Biological source: Lyngbya majuscula
• Total number of polymer chains: 1
• Total formula weight: 11009.31

Authors

Busche, A.E.,Gottstein, D.,Hein, C.,Ripin, N.,Pader, I.,Tufar, P.,Eisman, E.B.,Gu, L.,Walsh, C.T.,Loehr, F.,Sherman, D.H.,Guntert, P.,Dotsch, V. (deposition date: 2011-09-01, release date: 2011-12-14, Last modification date: 2024-05-15)

Primary citation

Busche, A.,Gottstein, D.,Hein, C.,Ripin, N.,Pader, I.,Tufar, P.,Eisman, E.B.,Gu, L.,Walsh, C.T.,Sherman, D.H.,Lohr, F.,Guntert, P.,Dotsch, V.
Characterization of Molecular Interactions between ACP and Halogenase Domains in the Curacin A Polyketide Synthase.
Acs Chem.Biol., 7:378-386, 2012

PubMed Abstract: Polyketide synthases (PKSs) and non-ribosomal peptide synthetases (NRPSs) 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(I)-ACP(II)-ACP(III)) within the CurA PKS module. We have determined the structure of the isolated holo-ACP(I) 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(I), 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(I) and form a contiguous surface. Since the CurA Hal accepts substrate only when presented by one of the ACPs within the ACP(I)-ACP(II)-ACP(III) tridomain, our data provide insight into the specificity of the chlorination reaction.

PubMed: 22103656
DOI: 10.1021/cb200352q

Experimental method

SOLUTION NMR