4NTN

E.coli QueD, SeMet protein, 2A resolution

Summary for 4NTN

• Entry DOI: 10.2210/pdb4ntn/pdb
• Related: 4NTK 4NTM
• Descriptor: 6-carboxy-5,6,7,8-tetrahydropterin synthase, ZINC ION, FORMIC ACID, ... (4 entities in total)
• Functional Keywords: t-fold, 6-ptps, queuosine biosynthesis enzyme, sepiapterin, lyase
• Biological source: Escherichia coli
• Total number of polymer chains: 6
• Total formula weight: 84321.25

Authors

Bandarian, V.,Roberts, S.A.,Miles, Z.D. (deposition date: 2013-12-02, release date: 2014-07-16, Last modification date: 2024-11-27)

Primary citation

Miles, Z.D.,Roberts, S.A.,McCarty, R.M.,Bandarian, V.
Biochemical and Structural Studies of 6-Carboxy-5,6,7,8-tetrahydropterin Synthase Reveal the Molecular Basis of Catalytic Promiscuity within the Tunnel-fold Superfamily.
J.Biol.Chem., 289:23641-23652, 2014

PubMed Abstract: 6-Pyruvoyltetrahydropterin synthase (PTPS) homologs in both mammals and bacteria catalyze distinct reactions using the same 7,8-dihydroneopterin triphosphate substrate. The mammalian enzyme converts 7,8-dihydroneopterin triphosphate to 6-pyruvoyltetrahydropterin, whereas the bacterial enzyme catalyzes the formation of 6-carboxy-5,6,7,8-tetrahydropterin. To understand the basis for the differential activities we determined the crystal structure of a bacterial PTPS homolog in the presence and absence of various ligands. Comparison to mammalian structures revealed that although the active sites are nearly structurally identical, the bacterial enzyme houses a His/Asp dyad that is absent from the mammalian protein. Steady state and time-resolved kinetic analysis of the reaction catalyzed by the bacterial homolog revealed that these residues are responsible for the catalytic divergence. This study demonstrates how small variations in the active site can lead to the emergence of new functions in existing protein folds.

PubMed: 24990950
DOI: 10.1074/jbc.M114.555680

Experimental method

X-RAY DIFFRACTION (1.99 Å)