PDBsum entry 4tts

Oxidoreductase

PDB id: 4tts

Contents

Protein chain

308 a.a.

Ligands

6DD

Waters ×288

PDB id:

4tts

Name:

Oxidoreductase

Title:

Crystal structure of the hydrolase domain of 10-formyltetrahydrofolate dehydrogenase (y200a) complex with 10-formyl-5,8-dideazafolate

Structure:

10-formyltetrahydrofolate dehydrogenase. Chain: a. Fragment: unp residues 1-311. Engineered: yes

Source:

Danio rerio. Zebrafish. Organism_taxid: 7955. Gene: aldh1l1. Expressed in: escherichia coli. Expression_system_taxid: 562

Resolution:

2.00Å R-factor: 0.204 R-free: 0.247

Authors:

C.C.Lin,C.J.Chen,T.F.Fu,P.Chuankhayan,T.T.Kao,W.N.Chang

Key ref:

C.C.Lin et al. (2015). Structures of the hydrolase domain of zebrafish 10-formyltetrahydrofolate dehydrogenase and its complexes reveal a complete set of key residues for hydrolysis and product inhibition. Acta Crystallogr D Biol Crystallogr, 71, 1006-1021. PubMed id: 25849409 DOI: 10.1107/S1399004715002928

Date:

23-Jun-14 Release date: 15-Apr-15

Protein chain

E3NZ06  (E3NZ06_DANRE) -  10-formyltetrahydrofolate dehydrogenase from Danio rerio

Seq: 903 a.a.

Struc: 308 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

Enzyme reactions

• Enzyme class: E.C.1.5.1.6 - formyltetrahydrofolate dehydrogenase.
• Pathway: Folate Coenzymes
• Reaction: (6R)-10-formyltetrahydrofolate + NADP⁺ + H2O = (6S)-5,6,7,8- tetrahydrofolate + CO2 + NADPH + H⁺

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

DOI no: 10.1107/S1399004715002928

Acta Crystallogr D Biol Crystallogr 71:1006-1021 (2015)

PubMed id: 25849409

Structures of the hydrolase domain of zebrafish 10-formyltetrahydrofolate dehydrogenase and its complexes reveal a complete set of key residues for hydrolysis and product inhibition.

C.C.Lin, P.Chuankhayan, W.N.Chang, T.T.Kao, H.H.Guan, H.K.Fun, A.Nakagawa, T.F.Fu, C.J.Chen.

ABSTRACT

10-Formyltetrahydrofolate dehydrogenase (FDH), which is composed of a small N-terminal domain (Nt-FDH) and a large C-terminal domain, is an abundant folate enzyme in the liver and converts 10-formyltetrahydrofolate (10-FTHF) to tetrahydrofolate (THF) and CO2. Nt-FDH alone possesses a hydrolase activity, which converts 10-FTHF to THF and formate in the presence of β-mercaptoethanol. To elucidate the catalytic mechanism of Nt-FDH, crystal structures of apo-form zNt-FDH from zebrafish and its complexes with the substrate analogue 10-formyl-5,8-dideazafolate (10-FDDF) and with the products THF and formate have been determined. The structures reveal that the conformations of three loops (residues 86-90, 135-143 and 200-203) are altered upon ligand (10-FDDF or THF) binding in the active site. The orientations and geometries of key residues, including Phe89, His106, Arg114, Asp142 and Tyr200, are adjusted for substrate binding and product release during catalysis. Among them, Tyr200 is especially crucial for product release. An additional potential THF binding site is identified in the cavity between two zNt-FDH molecules, which might contribute to the properties of product inhibition and THF storage reported for FDH. Together with mutagenesis studies and activity assays, the structures of zNt-FDH and its complexes provide a coherent picture of the active site and a potential THF binding site of zNt-FDH along with the substrate and product specificity, lending new insights into the molecular mechanism underlying the enzymatic properties of Nt-FDH.