PDBsum entry 4kln

Hydrolase

PDB id: 4kln

Contents

Protein chains

(+ 0 more) 451 a.a.

Ligands

AGS ×6

Metals

_MG ×6

Waters ×166

PDB id:

4kln

Name:

Hydrolase

Title:

Structure of p97 n-d1 a232e mutant in complex with atpgs

Structure:

Transitional endoplasmic reticulum atpase. Chain: a, b, c, d, e, f. Fragment: unp residue 1-481. Synonym: ter atpase, 15s mg(2+)-atpase p97 subunit, valosin- containing protein, vcp. Engineered: yes. Mutation: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Strain: human. Gene: p97, vcp. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

2.62Å R-factor: 0.275 R-free: 0.289

Authors:

D.Xia,W.K.Tang

Key ref:

W.K.Tang and D.Xia (2013). Altered intersubunit communication is the molecular basis for functional defects of pathogenic p97 mutants. J Biol Chem, 288, 36624-36635. PubMed id: 24196964 DOI: 10.1074/jbc.M113.488924

Date:

07-May-13 Release date: 13-Nov-13

Protein chains

P55072  (TERA_HUMAN) -  Transitional endoplasmic reticulum ATPase from Homo sapiens

Seq: 806 a.a.

Struc: 451 a.a.*

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

Enzyme reactions

• Enzyme class: E.C.3.6.4.6 - vesicle-fusing ATPase.
• Reaction: ATP + H2O = ADP + phosphate + H⁺

ATP (Bound ligand (Het Group name = AGS) matches with 93.75% similarity) + H2O = ADP + phosphate + H(+)

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

reference

DOI no: 10.1074/jbc.M113.488924

J Biol Chem 288:36624-36635 (2013)

PubMed id: 24196964

Altered intersubunit communication is the molecular basis for functional defects of pathogenic p97 mutants.

W.K.Tang, D.Xia.

ABSTRACT

The human AAA ATPase p97 is a molecular chaperone essential in cellular proteostasis. Single amino acid substitutions in p97 have been linked to a clinical multiple-disorder condition known as inclusion body myopathy associated with Paget's disease of the bone and frontotemporal dementia. How the mutations affect the molecular mechanism that governs the function of p97 remains unclear. Here, we show that within the hexameric ring of a mutant p97, D1 domains fail to regulate their respective nucleotide-binding states, as evidenced by the lower amount of prebound ADP, weaker ADP binding affinity, full occupancy of adenosine-5'-O-(3-thiotriphosphate) binding, and elevated overall ATPase activity, indicating a loss of communication among subunits. Defective communication between subunits is further illustrated by altered conformation in the side chain of residue Phe-360 that probes into the nucleotide-binding pocket from a neighboring subunit. Consequently, conformations of N domains in a hexameric ring of a mutant p97 become uncoordinated, thus impacting its ability to process substrate.