PDBsum entry 1j04

Transferase

PDB id: 1j04

Contents

Protein chain

387 a.a. *

Ligands

AOA

GOL ×7

Waters ×113

* Residue conservation analysis

PDB id:

1j04

Name:

Transferase

Title:

Structural mechanism of enzyme mistargeting in hereditary kidney stone disease in vitro

Structure:

Alanine--glyoxylate aminotransferase. Chain: a. Synonym: serine--pyruvate aminotransferase. Engineered: yes. Mutation: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562.

Biol. unit:

Dimer (from PQS)

Resolution:

2.60Å R-factor: 0.223 R-free: 0.273

Authors:

X.Zhang,S.Djordjevic,M.Bartlam,S.Ye,Z.Rao,C.J.Danpure

Key ref:

S.Djordjevic et al. (2010). Structural implications of a G170R mutation of alanine:glyoxylate aminotransferase that is associated with peroxisome-to-mitochondrion mistargeting. Acta Crystallogr Sect F Struct Biol Cryst Commun, 66, 233-236. PubMed id: 20208150

Date:

30-Oct-02 Release date: 11-Nov-03

Protein chain

P21549  (SPYA_HUMAN) -  Alanine--glyoxylate aminotransferase from Homo sapiens

Seq: 392 a.a.

Struc: 387 a.a.*

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

Enzyme reactions

• Enzyme class 1: E.C.2.6.1.44 - alanine--glyoxylate transaminase.
• Reaction: glyoxylate + L-alanine = glycine + pyruvate

glyoxylate (Bound ligand (Het Group name = AOA) matches with 83.33% similarity) + L-alanine = glycine + pyruvate

• Cofactor: Pyridoxal 5'-phosphate
• Enzyme class 2: E.C.2.6.1.51 - serine--pyruvate transaminase.
• Reaction: L-serine + pyruvate = 3-hydroxypyruvate + L-alanine

L-serine + pyruvate (Bound ligand (Het Group name = AOA) matches with 71.43% similarity) = 3-hydroxypyruvate (Bound ligand (Het Group name = GOL) matches with 85.71% similarity) + L-alanine

• Cofactor: Pyridoxal 5'-phosphate

Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.

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

reference

Acta Crystallogr Sect F Struct Biol Cryst Commun 66:233-236 (2010)

PubMed id: 20208150

Structural implications of a G170R mutation of alanine:glyoxylate aminotransferase that is associated with peroxisome-to-mitochondrion mistargeting.

S.Djordjevic, X.Zhang, M.Bartlam, S.Ye, Z.Rao, C.J.Danpure.

ABSTRACT

In a subset of patients with the hereditary kidney-stone disease primary hyperoxaluria type 1 (PH1), the liver-specific enzyme alanine:glyoxylate aminotransferase (AGT) is mistargeted from peroxisomes to mitochondria. This is a consequence of the combined presence of the common P11L polymorphism and a disease-specific G170R mutation. In this paper, the crystal structure of mutant human AGT containing the G170R replacement determined at a resolution of 2.6 A is reported. The crystal structure of AGT consists of an intimate dimer in which an extended N-terminal segment of 21 amino acids from one subunit wraps as an elongated irregular coil around the outside of the crystallographic symmetry-related subunit. In addition to the N-terminal segment, the monomer structure contains a large domain of 261 amino acids and a small C-terminal domain of 110 amino acids. Comparison of the mutant AGT structure and that of wild-type normal AGT shows that the two structures are almost identical, with a backbone-atom r.m.s. deviation of 0.34 A. However, evidence of significant local structural changes in the vicinity of the G170R mutation might be linked to the apparent decrease in protein stability.