Solution structure and proposed domain domain recognition interface of an acyl carrier protein domain from a modular polyketide synthase.

Solution structure and proposed domain domain recognition interface of an acyl carrier protein domain from a modular polyketide synthase. Research Abstract Details 

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Solution structure and proposed domain domain recognition interface of an acyl carrier protein domain from a modular polyketide synthase. Abstract Text:

Viktor Y Alekseyev,Corey W Liu,David E Cane,Joseph D Puglisi,Chaitan Khosla,

Polyketides are a medicinally important class of natural products. The architecture of modular polyketide synthases (PKSs), composed of multiple covalently linked domains grouped into modules, provides an attractive framework for engineering novel polyketide-producing assemblies. However, impaired domain-domain interactions can compromise the efficiency of engineered polyketide biosynthesis. To facilitate the study of these domain-domain interactions, we have used nuclear magnetic resonance (NMR) spectroscopy to determine the first solution structure of an acyl carrier protein (ACP) domain from a modular PKS, 6-deoxyerythronolide B synthase (DEBS). The tertiary fold of this 10-kD domain is a three-helical bundle; an additional short helix in the second loop also contributes to the core helical packing. Superposition of residues 14-94 of the ensemble on the mean structure yields an average atomic RMSD of 0.64 +/- 0.09 Angstrom for the backbone atoms (1.21 +/- 0.13 Angstrom for all non-hydrogen atoms). The three major helices superimpose with a backbone RMSD of 0.48 +/- 0.10 Angstrom (0.99 +/- 0.11 Angstrom for non-hydrogen atoms). Based on this solution structure, homology models were constructed for five other DEBS ACP domains. Comparison of their steric and electrostatic surfaces at the putative interaction interface (centered on helix II) suggests a model for protein-protein recognition of ACP domains, consistent with the previously observed specificity. Site-directed mutagenesis experiments indicate that two of the identified residues influence the specificity of ACP recognition.

Solution structure and proposed domain domain recognition interface of an acyl carrier protein domain from a modular polyketide synthase. Publishing Authors By Initials

VY Alekseyev,CW Liu,DE Cane,JD Puglisi,C Khosla,

For similar biochemical phenomena, metabolism, and nutrition: biochemical phenomena: molecular structure: molecular conformation: protein conformation: structural homology, protein research abstracts see: biochemical phenomena, metabolism, and nutrition: biochemical phenomena: molecular structure: molecular conformation: protein conformation: structural homology, protein research

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MEDLINE DATE:

Solution structure and proposed domain domain recognition interface of an acyl carrier protein domain from a modular polyketide synthase. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Protein science : a publication of the Protein Soc

VOLUME: 16

Page Numbers: 2093-107

Journal Abbreviation: Protein Sci.

ISSN: 0961-8368

DAY: 3

MONTH: Oct

YEAR: 2007

Solution structure and proposed domain domain recognition interface of an acyl carrier protein domain from a modular polyketide synthase. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 9211750

Solution structure and proposed domain domain recognition interface of an acyl carrier protein domain from a modular polyketide synthase. Keywords Mesh Terms:

KEYWORDS: Structural Homology, Protein

MESH TERMS: genetics

Chemical & Substance for Abstract: Solution structure and proposed domain domain recognition interface of an acyl carrier protein domain from a modular polyketide synthase. Information

Substance Name: erythomycin A biosynthesis hydrolase

Registry Number: EC 1.-.

Grant and Affiliation Information for Solution structure and proposed domain domain recognition interface of an acyl carrier protein domain from a modular polyketide synthase.

AFFILIATION: Department of Chemistry, Stanford University, Stanford, California 94305, USA.

Country: United States

AGENCY: United States NCI

GRANT: CA 66736

ACRONYM: CA

MEDLINETA: Protein Sci

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