Atomic structure of the cubic core of the pyruvate dehydrogenase multienzyme complex.
The highly symmetric pyruvate dehydrogenase multienzyme complexes have molecular masses ranging from 5 to 10 million daltons. They consist of numerous copies of three different enzymes: pyruvate dehydrogenase, dihydrolipoyl transacetylase, and lipoamide dehydrogenase. The three-dimensional crystal structure of the catalytic domain of Azotobacter vinelandii dihydrolipoyl transacetylase has been determined at 2.6 angstrom (A) resolution. Eight trimers assemble as a hollow truncated cube with an edge of 125 A, forming the core of the multienzyme complex. Coenzyme A must enter the 29 A long active site channel from the inside of the cube, and lipoamide must enter from the outside. The trimer of the catalytic domain of dihydrolipoyl transacetylase has a topology identical to chloramphenicol acetyl transferase. The atomic structure of the 24-subunit cube core provides a framework for understanding all pyruvate dehydrogenase and related multienzyme complexes.
Mattevi
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A
Department of Chemistry, University of Groningen, The Netherlands.
Obmolova
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G
Schulze
E
E
Kalk
K H
KH
Westphal
A H
AH
de Kok
A
A
Hol
W G
WG
D000595:Amino Acid Sequence; D000818:Animals; D016948:Azotobacter vinelandii / Q000201:enzymology; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015394:Molecular Structure; D011768:Pyruvate Dehydrogenase Complex / Q000737:chemistry* / Q000235:genetics; D012689:Sequence Homology, Nucleic Acid
D011768:Pyruvate Dehydrogenase Complex; D015500:Chloramphenicol O-Acetyltransferase