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Identification of functional paralog shift mutations: conversion of Escherichia coli malate dehydrogenase to a lactate dehydrogenase.

Identification of functional paralog shift mutations: conversion of Escherichia coli malate dehydrogenase to a lactate dehydrogenase. Research Abstract Details 

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  • Identification of functional paralog shift mutations: conversion of Escherichia coli malate dehydrogenase to a lactate dehydrogenase. Abstract Text:

    yifeng yinYifeng Yin,jack f kirschJack F Kirsch,yifeng yinYifeng Yin,jack f kirschJack F Kirsch,

    Five positions in the Escherichia coli malate dehydrogenase (eMDH) sequence, which distinguish MDH from lactate dehydrogenase (LDH) activity, were identified through a combination of Venn diagrams constructed from whole genomic data and from unbiased representative sequences from terminal clades. Incorporation of the five changes in eMDH sufficed to convert the enzyme from one with (k(cat)/K(m)(pyruvate))/(k(cat)/K(m)(oxaloacetate)) = 6.1 x 10(-9) to one with that ratio = 28. The substrate specificity was thus changed by a factor of 4.6 x 10(9). The k(cat)/K(m)(pyruvate) value for the pentamutant (eMDH I12V/R81Q/M85E/G210A/V214I) is 3,500 M(-1).s(-1), which is approximately equal 1/1,000 of the values found for typical wild-type LDHs. The procedure isolates an intersection of "strong forcing sets" that should prove to be of general use in switching paralog function.

    Identification of functional paralog shift mutations: conversion of Escherichia coli malate dehydrogenase to a lactate dehydrogenase. Publishing Authors By Initials

    y yinY Yin,jf kirschJF Kirsch,y yinY Yin,jf kirschJF Kirsch,

    For similar abstracts research abstracts see: abstracts research

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    Identification of functional paralog shift mutations: conversion of Escherichia coli malate dehydrogenase to a lactate dehydrogenase. Journal Published:

    PUBLICATION TYPE: Research Support, N.I.H., Extr

    Journal: Proceedings of the National Academy of Sciences of

    VOLUME: 104

    Page Numbers: 17353-7

    Journal Abbreviation: Proc. Natl. Acad. Sci. U.S.A.

    ISSN: 0027-8424

    DAY: 18

    MONTH: 10

    YEAR: 2007

    Identification of functional paralog shift mutations: conversion of Escherichia coli malate dehydrogenase to a lactate dehydrogenase. Information

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    LANGUAGE: eng

    NlmUniqueID: 7505876

    Identification of functional paralog shift mutations: conversion of Escherichia coli malate dehydrogenase to a lactate dehydrogenase. Keywords Mesh Terms:

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    Grant and Affiliation Information for Identification of functional paralog shift mutations: conversion of Escherichia coli malate dehydrogenase to a lactate dehydrogenase.

    AFFILIATION: QB3 Institute, 572 Stanley Hall, University of California, Berkeley, CA 94720-3220, USA.

    Country: United States

    United States Research PublicationUnited States Research Publication

    AGENCY: United States NIGMS

    GRANT: GM35393

    ACRONYM: GM

    MEDLINETA: Proc Natl Acad Sci U S A

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