PDBsum entry 4kyo

Transferase/transport protein

PDB id: 4kyo

Contents

Protein chains

387 a.a.

286 a.a.

Ligands

SO4 ×2

BTB ×2

BME ×12

Waters ×709

PDB id:

4kyo

Name:

Transferase/transport protein

Title:

Alanine-glyoxylate aminotransferase variant k390a in complex with the tpr domain of human pex5p

Structure:

Serine-pyruvate aminotransferase. Chain: a, c. Synonym: spt, alanine--glyoxylate aminotransferase, agt. Engineered: yes. Mutation: yes. Peroxisomal targeting signal 1 receptor. Chain: b, d. Fragment: tpr domain, unp residues 315-639. Synonym: pts1 receptor, pts1r, pts1-bp, peroxin-5, peroxisomal c-

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: agxt, agt1, spat. Expressed in: escherichia coli. Expression_system_taxid: 469008. Gene: pex5, pxr1.

Resolution:

2.20Å R-factor: 0.177 R-free: 0.218

Authors:

K.Fodor,Y.Lou,M.Wilmanns

Key ref:

K.Fodor et al. (2015). Ligand-induced compaction of the PEX5 receptor-binding cavity impacts protein import efficiency into peroxisomes. Traffic, 16, 85-98. PubMed id: 25369882 DOI: 10.1111/tra.12238

Date:

29-May-13 Release date: 19-Nov-14

Protein chains

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

Seq: 392 a.a.

Struc: 387 a.a.*

Protein chains

P50542  (PEX5_HUMAN) -  Peroxisomal targeting signal 1 receptor from Homo sapiens

Seq: 639 a.a.

Struc: 286 a.a.

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

Enzyme reactions

• Enzyme class 2: Chains A, C: E.C.2.6.1.44 - alanine--glyoxylate transaminase.
• Reaction: glyoxylate + L-alanine = glycine + pyruvate

glyoxylate (Bound ligand (Het Group name = BME) matches with 50.00% similarity) + L-alanine = glycine + pyruvate

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

L-serine (Bound ligand (Het Group name = BTB) matches with 40.00% similarity) + pyruvate (Bound ligand (Het Group name = BME) matches with 42.86% similarity) = 3-hydroxypyruvate + 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

DOI no: 10.1111/tra.12238

Traffic 16:85-98 (2015)

PubMed id: 25369882

Ligand-induced compaction of the PEX5 receptor-binding cavity impacts protein import efficiency into peroxisomes.

K.Fodor, J.Wolf, K.Reglinski, D.M.Passon, Y.Lou, W.Schliebs, R.Erdmann, M.Wilmanns.

ABSTRACT

Peroxisomes entirely rely on the import of their proteome across the peroxisomal membrane. Recognition efficiencies of peroxisomal proteins vary by more than 1000-fold, but the molecular rationale behind their subsequent differential import and sorting has remained enigmatic. Using the protein cargo alanine-glyoxylate aminotransferase as a model, an unexpected increase from 34 to 80% in peroxisomal import efficiency of a single-residue mutant has been discovered. By high-resolution structural analysis, we found that it is the recognition receptor PEX5 that adapts its conformation for high-affinity binding rather than the cargo protein signal motif as previously thought. During receptor recognition, the binding cavity of the receptor shrinks to one third of its original volume. This process is impeded in the wild-type protein cargo because of a bulky side chain within the recognition motif, which blocks contraction of the PEX5 binding cavity. Our data provide a new insight into direct protein import efficiency by removal rather than by addition of an apparent specific sequence signature that is generally applicable to peroxisomal matrix proteins and to other receptor recognition processes.