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Structural studies of tri-functional human GART.

ABSTRACT: Human purine de novo synthesis pathway contains several multi-functional enzymes, one of which, tri-functional GART, contains three enzymatic activities in a single polypeptide chain. We have solved structures of two domains bearing separate catalytic functions: glycinamide ribonucleotide synthetase and aminoimidazole ribonucleotide synthetase. Structures are compared with those of homologous enzymes from prokaryotes and analyzed in terms of the catalytic mechanism. We also report small angle X-ray scattering models for the full-length protein. These models are consistent with the enzyme forming a dimer through the middle domain. The protein has an approximate seesaw geometry where terminal enzyme units display high mobility owing to flexible linker segments. This resilient seesaw shape may facilitate internal substrate/product transfer or forwarding to other enzymes in the pathway.

SUBMITTER: Welin M

PROVIDER: S-EPMC2978367 | biostudies-literature | 2010 Nov

REPOSITORIES: biostudies-literature

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Structural studies of tri-functional human GART.

Welin Martin M Grossmann Jörg Günter JG Flodin Susanne S Nyman Tomas T Stenmark Pål P Trésaugues Lionel L Kotenyova Tetyana T Johansson Ida I Nordlund Pär P Lehtiö Lari L

Nucleic acids research 20100714 20

Human purine de novo synthesis pathway contains several multi-functional enzymes, one of which, tri-functional GART, contains three enzymatic activities in a single polypeptide chain. We have solved structures of two domains bearing separate catalytic functions: glycinamide ribonucleotide synthetase and aminoimidazole ribonucleotide synthetase. Structures are compared with those of homologous enzymes from prokaryotes and analyzed in terms of the catalytic mechanism. We also report small angle X- ...[more]

PMID: 20631005

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Structural studies of tri-functional human GART.

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Structural studies of tri-functional human GART.

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