Structure of the Pyruvate Dehydrogenase Multienzyme Complex E1 Component from Escherichia coli at 1.85 Å Resolution
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- 作者：Palaniappa Arjunan ; Natalia Nemeria ; Andrew Brunskill ; Krishnamoorthy Chandrasekhar ; Martin Sax ; Yan Yan ; Frank Jordan ; John R. Guest ; and William Furey
- 刊名：Biochemistry
- 出版年：2002
- 出版时间：April 23, 2002
- 年：2002
- 卷：41
- 期：16
- 页码：5213 - 5221
- 全文大小：698K
- 年卷期：v.41,no.16(April 23, 2002)
- ISSN：1520-4995
文摘
The crystal structure of the recombinant thiamin diphosphate-dependent E1 component fromthe Escherichia coli pyruvate dehydrogenase multienzyme complex (PDHc) has been determined at aresolution of 1.85 Å. The E. coli PDHc E1 component E1p is a homodimeric enzyme and crystallizeswith an intact dimer in an asymmetric unit. Each E1p subunit consists of three domains: N-terminal,middle, and C-terminal, with all having 
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folds. The functional dimer contains two catalytic centerslocated at the interface between subunits. The ThDP cofactors are bound in the "V" conformation inclefts between the two subunits (binding involves the N-terminal and middle domains), and there is acommon ThDP binding fold. The cofactors are completely buried, as only the C2 atoms are accessiblefrom solution through the active site clefts. Significant structural differences are observed between individualdomains of E1p relative to heterotetrameric multienzyme complex E1 components operating on branchedchain substrates. These differences may be responsible for reported alternative E1p binding modes to E2components within the respective complexes. This paper represents the first structural example of afunctional pyruvate dehydrogenase E1p component from any species. It also provides the first representative example for the entire family of homodimeric (2) E1 multienzyme complex components, and shouldserve as a model for this class of enzymes.
/ folds. The functional dimer contains two catalytic centerslocated at the interface between subunits. The ThDP cofactors are bound in the "V" conformation inclefts between the two subunits (binding involves the N-terminal and middle domains), and there is acommon ThDP binding fold. The cofactors are completely buried, as only the C2 atoms are accessiblefrom solution through the active site clefts. Significant structural differences are observed between individualdomains of E1p relative to heterotetrameric multienzyme complex E1 components operating on branchedchain substrates. These differences may be responsible for reported alternative E1p binding modes to E2components within the respective complexes. This paper represents the first structural example of afunctional pyruvate dehydrogenase E1p component from any species. It also provides the first representative example for the entire family of homodimeric (2) E1 multienzyme complex components, and shouldserve as a model for this class of enzymes.