PDBsum entry 4pxc

Hydrolase

PDB id: 4pxc

Contents

Protein chains

423 a.a.

Ligands

HGY ×2

Metals

_MN ×4

Waters ×1133

PDB id:

4pxc

Name:

Hydrolase

Title:

The crystal structure of atuah in complex with (s)-hydroxyglycine

Structure:

Ureidoglycolate hydrolase. Chain: a, b. Fragment: unp residues 50-476. Synonym: atuah, allantoate amidohydrolase 2, atahh2, ureidoglycolate amidohydrolase. Engineered: yes. Mutation: yes

Source:

Arabidopsis thaliana. Mouse-ear cress,thale-cress. Organism_taxid: 3702. Gene: uah, aah2, at5g43600, k9d7.10. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

1.89Å R-factor: 0.169 R-free: 0.195

Authors:

I.Shin,S.Rhee

Key ref:

I.Shin et al. (2014). Structural insights into the substrate specificity of (s)-ureidoglycolate amidohydrolase and its comparison with allantoate amidohydrolase. J Mol Biol, 426, 3028-3040. PubMed id: 25020232 DOI: 10.1016/j.jmb.2014.06.017

Date:

23-Mar-14 Release date: 23-Jul-14

Protein chains

Q8VXY9  (UAH_ARATH) -  Ureidoglycolate hydrolase from Arabidopsis thaliana

Seq: 476 a.a.

Struc: 423 a.a.*

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

Enzyme reactions

• Enzyme class: E.C.3.5.1.116 - ureidoglycolate amidohydrolase.
• Reaction: (S)-ureidoglycolate + H2O + 2 H⁺ = glyoxylate + 2 NH4⁺ + CO2

(S)-ureidoglycolate + H2O + 2 × H(+) = glyoxylate + 2 × NH4(+) (Bound ligand (Het Group name = HGY) matches with 83.33% similarity) + CO2

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

reference

DOI no: 10.1016/j.jmb.2014.06.017

J Mol Biol 426:3028-3040 (2014)

PubMed id: 25020232

Structural insights into the substrate specificity of (s)-ureidoglycolate amidohydrolase and its comparison with allantoate amidohydrolase.

I.Shin, K.Han, S.Rhee.

ABSTRACT

In plants, the ureide pathway is a metabolic route that converts the ring nitrogen atoms of purine into ammonia via sequential enzymatic reactions, playing an important role in nitrogen recovery. In the final step of the pathway, (S)-ureidoglycolate amidohydrolase (UAH) catalyzes the conversion of (S)-ureidoglycolate into glyoxylate and releases two molecules of ammonia as by-products. UAH is homologous in structure and sequence with allantoate amidohydrolase (AAH), an upstream enzyme in the pathway with a similar function as that of an amidase but with a different substrate. Both enzymes exhibit strict substrate specificity and catalyze reactions in a concerted manner, resulting in purine degradation. Here, we report three crystal structures of Arabidopsis thaliana UAH (bound with substrate, reaction intermediate, and product) and a structure of Escherichia coli AAH complexed with allantoate. Structural analyses of UAH revealed a distinct binding mode for each ligand in a bimetal reaction center with the active site in a closed conformation. The ligand directly participates in the coordination shell of two metal ions and is stabilized by the surrounding residues. In contrast, AAH, which exhibits a substrate-binding site similar to that of UAH, requires a larger active site due to the additional ureido group in allantoate. Structural analyses and mutagenesis revealed that both enzymes undergo an open-to-closed conformational transition in response to ligand binding and that the active-site size and the interaction environment in UAH and AAH are determinants of the substrate specificities of these two structurally homologous enzymes.