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Crystal Structures and Mutational Analyses of Acyl-CoA Carboxylase β Subunit of Streptomyces coelicolor.

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Title: Crystal Structures and Mutational Analyses of Acyl-CoA Carboxylase β Subunit of Streptomyces coelicolor.
Authors: AraboIaza, Ana, Shillito, Mary Elizabeth1, Ting-Wan Lin1,2, Diacovich, Lautaro1, Melgar, Melrose2, Pham, Huy2, Amick, Deborah2, Gramajo, Hugo1 gramajo@ibr.gov.ar, Shiou-Chuan Tsai2
Source: Biochemistry. 8/31/2010, Vol. 49 Issue 34, p7367-7376. 11p.
Subjects: Streptomyces coelicolor, Biosynthesis, Genetic mutation, Fatty acid synthesis, Polyketides, Biotin, Actinobacteria
Abstract: The first committed step of fatty acid and polyketides biosynthesis, the biotin-dependent carboxylation of an acyl-CoA, is catalyzed by acyl-CoA carboxylases (ACCases) such as acetyl-CoA carboxylase (ACC) and propionyl-C0A carboxylase (PCC). ACC and PCC in Sireptornyces coelicolor are homologue multisubunit complexes that can carboxylate different short chain acyl-CoAs. While ACC is able to carboxylate acetyl-, propionyl-, or butyryl-CoA with approximately the same specificity, PCC only recognizes propionyland butyryl-CoA as substrates. How ACC and PCC have such different specificities toward these substrates is only partially understood. To further understand the molecular basis of how the active site residues can modulate the substrate recognition, we mutated D422, N80, R456, and R457 of PccB, the catalytic beta subunit of PCC. The crystal structures of six PccB mutants and the wild type crystal structure were compared systematically to establish the sequence-structure-function relationship that correlates the observed substrate specificity toward acetyl-, propionyl-, and butyryl-CoA with active site geometry. The experimental data confirmed that D422 is a key determinant of substrate specificity, influencing not only the active site properties but further altering protein stability and causing long-range conformational changes. Mutations of N80, R456, and R457 lead to variations in the quaternary structure of the beta subunit and to a concomitant loss of enzyme activity, indicating the importance of these residues in maintaining the active protein conformation as well as a critical role in substrate binding. [ABSTRACT FROM AUTHOR]
Copyright of Biochemistry is the property of American Chemical Society and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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DbLabel: Engineering Source
An: 53431224
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  Label: Title
  Group: Ti
  Data: Crystal Structures and Mutational Analyses of Acyl-CoA Carboxylase β Subunit of Streptomyces coelicolor.
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  Data: <searchLink fieldCode="AR" term="%22AraboIaza%2C+Ana%22">AraboIaza, Ana</searchLink><br /><searchLink fieldCode="AR" term="%22Shillito%2C+Mary+Elizabeth%22">Shillito, Mary Elizabeth</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Ting-Wan+Lin%22">Ting-Wan Lin</searchLink><relatesTo>1,2</relatesTo><br /><searchLink fieldCode="AR" term="%22Diacovich%2C+Lautaro%22">Diacovich, Lautaro</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Melgar%2C+Melrose%22">Melgar, Melrose</searchLink><relatesTo>2</relatesTo><br /><searchLink fieldCode="AR" term="%22Pham%2C+Huy%22">Pham, Huy</searchLink><relatesTo>2</relatesTo><br /><searchLink fieldCode="AR" term="%22Amick%2C+Deborah%22">Amick, Deborah</searchLink><relatesTo>2</relatesTo><br /><searchLink fieldCode="AR" term="%22Gramajo%2C+Hugo%22">Gramajo, Hugo</searchLink><relatesTo>1</relatesTo><i> gramajo@ibr.gov.ar</i><br /><searchLink fieldCode="AR" term="%22Shiou-Chuan+Tsai%22">Shiou-Chuan Tsai</searchLink><relatesTo>2</relatesTo>
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  Data: <searchLink fieldCode="JN" term="%22Biochemistry%22">Biochemistry</searchLink>. 8/31/2010, Vol. 49 Issue 34, p7367-7376. 11p.
– Name: Subject
  Label: Subjects
  Group: Su
  Data: <searchLink fieldCode="DE" term="%22Streptomyces+coelicolor%22">Streptomyces coelicolor</searchLink><br /><searchLink fieldCode="DE" term="%22Biosynthesis%22">Biosynthesis</searchLink><br /><searchLink fieldCode="DE" term="%22Genetic+mutation%22">Genetic mutation</searchLink><br /><searchLink fieldCode="DE" term="%22Fatty+acid+synthesis%22">Fatty acid synthesis</searchLink><br /><searchLink fieldCode="DE" term="%22Polyketides%22">Polyketides</searchLink><br /><searchLink fieldCode="DE" term="%22Biotin%22">Biotin</searchLink><br /><searchLink fieldCode="DE" term="%22Actinobacteria%22">Actinobacteria</searchLink>
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: The first committed step of fatty acid and polyketides biosynthesis, the biotin-dependent carboxylation of an acyl-CoA, is catalyzed by acyl-CoA carboxylases (ACCases) such as acetyl-CoA carboxylase (ACC) and propionyl-C0A carboxylase (PCC). ACC and PCC in Sireptornyces coelicolor are homologue multisubunit complexes that can carboxylate different short chain acyl-CoAs. While ACC is able to carboxylate acetyl-, propionyl-, or butyryl-CoA with approximately the same specificity, PCC only recognizes propionyland butyryl-CoA as substrates. How ACC and PCC have such different specificities toward these substrates is only partially understood. To further understand the molecular basis of how the active site residues can modulate the substrate recognition, we mutated D422, N80, R456, and R457 of PccB, the catalytic beta subunit of PCC. The crystal structures of six PccB mutants and the wild type crystal structure were compared systematically to establish the sequence-structure-function relationship that correlates the observed substrate specificity toward acetyl-, propionyl-, and butyryl-CoA with active site geometry. The experimental data confirmed that D422 is a key determinant of substrate specificity, influencing not only the active site properties but further altering protein stability and causing long-range conformational changes. Mutations of N80, R456, and R457 lead to variations in the quaternary structure of the beta subunit and to a concomitant loss of enzyme activity, indicating the importance of these residues in maintaining the active protein conformation as well as a critical role in substrate binding. [ABSTRACT FROM AUTHOR]
– Name: AbstractSuppliedCopyright
  Label:
  Group: Ab
  Data: <i>Copyright of Biochemistry is the property of American Chemical Society and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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        Value: 10.1021/bi1005305
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        Text: English
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        PageCount: 11
        StartPage: 7367
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      – SubjectFull: Streptomyces coelicolor
        Type: general
      – SubjectFull: Biosynthesis
        Type: general
      – SubjectFull: Genetic mutation
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      – SubjectFull: Fatty acid synthesis
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      – SubjectFull: Polyketides
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      – SubjectFull: Biotin
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      – SubjectFull: Actinobacteria
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      – TitleFull: Crystal Structures and Mutational Analyses of Acyl-CoA Carboxylase β Subunit of Streptomyces coelicolor.
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              Text: 8/31/2010
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