1WYV

Crystal structure of glycine decarboxylase (P-protein) of the glycine cleavage system, in inhibitor-bound form

Summary for 1WYV

• Entry DOI: 10.2210/pdb1wyv/pdb
• Related: 1WYT 1WYU
• Descriptor: glycine dehydrogenase (decarboxylating) subunit 1, glycine dehydrogenase subunit 2 (P-protein), PYRIDOXAL-5'-PHOSPHATE, ... (5 entities in total)
• Functional Keywords: alpha(2)beta(2) tetramer, riken structural genomics/proteomics initiative, rsgi, structural genomics, oxidoreductase
• Biological source: Thermus thermophilus; More
• Total number of polymer chains: 8
• Total formula weight: 401164.21

Authors

Nakai, T.,Nakagawa, N.,Maoka, N.,Masui, R.,Kuramitsu, S.,Kamiya, N.,RIKEN Structural Genomics/Proteomics Initiative (RSGI) (deposition date: 2005-02-17, release date: 2005-04-05, Last modification date: 2024-04-03)

Primary citation

Nakai, T.,Nakagawa, N.,Maoka, N.,Masui, R.,Kuramitsu, S.,Kamiya, N.
Structure of P-protein of the glycine cleavage system: implications for nonketotic hyperglycinemia
Embo J., 24:1523-1536, 2005

PubMed Abstract: The crystal structure of the P-protein of the glycine cleavage system from Thermus thermophilus HB8 has been determined. This is the first reported crystal structure of a P-protein, and it reveals that P-proteins do not involve the alpha(2)-type active dimer universally observed in the evolutionarily related pyridoxal 5'-phosphate (PLP)-dependent enzymes. Instead, novel alphabeta-type dimers associate to form an alpha(2)beta(2) tetramer, where the alpha- and beta-subunits are structurally similar and appear to have arisen by gene duplication and subsequent divergence with a loss of one active site. The binding of PLP to the apoenzyme induces large open-closed conformational changes, with residues moving up to 13.5 A. The structure of the complex formed by the holoenzyme bound to an inhibitor, (aminooxy)acetate, suggests residues that may be responsible for substrate recognition. The molecular surface around the lipoamide-binding channel shows conservation of positively charged residues, which are possibly involved in complex formation with the H-protein. These results provide insights into the molecular basis of nonketotic hyperglycinemia.

PubMed: 15791207
DOI: 10.1038/sj.emboj.7600632

Experimental method

X-RAY DIFFRACTION (2.4 Å)