PDBsum entry 5ftn

Hydrolase

PDB id: 5ftn

Contents

Protein chains

(+ 0 more) 737 a.a.

Ligands

AGS ×12

Metals

_MG ×12

PDB id:

5ftn

Name:

Hydrolase

Title:

Cryo-em structure of human p97 bound to atpgs (conformation iii)

Structure:

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

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 469008. Expression_system_variant: rosetta2

Authors:

S.Banerjee,A.Bartesaghi,A.Merk,P.Rao,S.L.Bulfer,Y.Yan,N.Green, B.Mroczkowski,R.J.Neitz,P.Wipf,V.Falconieri,R.J.Deshaies, J.L.S.Milne,D.Huryn,M.Arkin,S.Subramaniam

Key ref:

S.Banerjee et al. (2016). 2.3 Å resolution cryo-EM structure of human p97 and mechanism of allosteric inhibition. Science, 351, 871-875. PubMed id: 26822609 DOI: 10.1126/science.aad7974

Date:

14-Jan-16 Release date: 27-Jan-16

Protein chains

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

Seq: 806 a.a.

Struc: 737 a.a.

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: 10.1126/science.aad7974

Science 351:871-875 (2016)

PubMed id: 26822609

2.3 Å resolution cryo-EM structure of human p97 and mechanism of allosteric inhibition.

S.Banerjee, A.Bartesaghi, A.Merk, P.Rao, S.L.Bulfer, Y.Yan, N.Green, B.Mroczkowski, R.J.Neitz, P.Wipf, V.Falconieri, R.J.Deshaies, J.L.Milne, D.Huryn, M.Arkin, S.Subramaniam.

ABSTRACT

p97 is a hexameric AAA+ adenosine triphosphatase (ATPase) that is an attractive target for cancer drug development. We report cryo-electron microscopy (cryo-EM) structures for adenosine diphosphate (ADP)-bound, full-length, hexameric wild-type p97 in the presence and absence of an allosteric inhibitor at resolutions of 2.3 and 2.4 angstroms, respectively. We also report cryo-EM structures (at resolutions of ~3.3, 3.2, and 3.3 angstroms, respectively) for three distinct, coexisting functional states of p97 with occupancies of zero, one, or two molecules of adenosine 5'-O-(3-thiotriphosphate) (ATPγS) per protomer. A large corkscrew-like change in molecular architecture, coupled with upward displacement of the N-terminal domain, is observed only when ATPγS is bound to both the D1 and D2 domains of the protomer. These cryo-EM structures establish the sequence of nucleotide-driven structural changes in p97 at atomic resolution. They also enable elucidation of the binding mode of an allosteric small-molecule inhibitor to p97 and illustrate how inhibitor binding at the interface between the D1 and D2 domains prevents propagation of the conformational changes necessary for p97 function.