PDBsum entry 5mcp

Oxidoreductase

PDB id: 5mcp

Contents

Protein chains

440 a.a.

387 a.a.

342 a.a.

382 a.a.

321 a.a.

Ligands

ATP ×24

Metals

_MG ×8

Waters ×1276

PDB id:

5mcp

Name:

Oxidoreductase

Title:

Structure of imp dehydrogenase from ashbya gossypii bound to atp

Structure:

Inosine-5'-monophosphate dehydrogenase. Chain: a, b, c, d, e, f, g, h. Synonym: impdh. Engineered: yes

Source:

Ashbya gossypii (strain atcc 10895 / cbs 109.51 / fgsc 9923 / nrrl y-1056). Yeast. Organism_taxid: 284811. Strain: atcc 10895 / cbs 109.51 / fgsc 9923 / nrrl y-1056. Gene: agos_aer117w. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008

Resolution:

2.40Å R-factor: 0.251 R-free: 0.271

Authors:

G.Winter,D.Fernandez-Justel,J.M.De Pereda,J.L.Revuelta,R.M.Buey

Key ref:

R.M.Buey et al. (2017). A nucleotide-controlled conformational switch modulates the activity of eukaryotic IMP dehydrogenases. Sci Rep, 7, 2648. PubMed id: 28572600

Date:

10-Nov-16 Release date: 14-Jun-17

Protein chains

Q756Z6  (Q756Z6_ASHGO) -  Inosine-5'-monophosphate dehydrogenase from Eremothecium gossypii (strain ATCC 10895 / CBS 109.51 / FGSC 9923 / NRRL Y-1056)

Seq: 522 a.a.

Struc: 440 a.a.

Protein chain

Q756Z6  (Q756Z6_ASHGO) -  Inosine-5'-monophosphate dehydrogenase from Eremothecium gossypii (strain ATCC 10895 / CBS 109.51 / FGSC 9923 / NRRL Y-1056)

Seq: 522 a.a.

Struc: 387 a.a.*

Protein chain

Q756Z6  (Q756Z6_ASHGO) -  Inosine-5'-monophosphate dehydrogenase from Eremothecium gossypii (strain ATCC 10895 / CBS 109.51 / FGSC 9923 / NRRL Y-1056)

Seq: 522 a.a.

Struc: 342 a.a.

Protein chain

Q756Z6  (Q756Z6_ASHGO) -  Inosine-5'-monophosphate dehydrogenase from Eremothecium gossypii (strain ATCC 10895 / CBS 109.51 / FGSC 9923 / NRRL Y-1056)

Seq: 522 a.a.

Struc: 382 a.a.

Protein chain

Q756Z6  (Q756Z6_ASHGO) -  Inosine-5'-monophosphate dehydrogenase from Eremothecium gossypii (strain ATCC 10895 / CBS 109.51 / FGSC 9923 / NRRL Y-1056)

Seq: 522 a.a.

Struc: 321 a.a.

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

Enzyme reactions

• Enzyme class: Chains A, B, C, D, E, F, G, H: E.C.1.1.1.205 - Imp dehydrogenase.
• Pathway: AMP and GMP Biosynthesis
• Reaction: IMP + NAD⁺ + H2O = XMP + NADH + H⁺

IMP + NAD(+) (Bound ligand (Het Group name = ATP) matches with 68.75% similarity) + H2O = XMP + NADH + H(+)

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

reference

Sci Rep 7:2648 (2017)

PubMed id: 28572600

A nucleotide-controlled conformational switch modulates the activity of eukaryotic IMP dehydrogenases.

R.M.Buey, D.Fernández-Justel, �.�.Marcos-Alcalde, G.Winter, P.Gómez-Puertas, J.M.de Pereda, J.Luis Revuelta.

ABSTRACT

Inosine-5'-monophosphate dehydrogenase (IMPDH) is an essential enzyme for nucleotide metabolism and cell proliferation. Despite IMPDH is the target of drugs with antiviral, immunosuppressive and antitumor activities, its physiological mechanisms of regulation remain largely unknown. Using the enzyme from the industrial fungus Ashbya gossypii, we demonstrate that the binding of adenine and guanine nucleotides to the canonical nucleotide binding sites of the regulatory Bateman domain induces different enzyme conformations with significantly distinct catalytic activities. Thereby, the comparison of their high-resolution structures defines the mechanistic and structural details of a nucleotide-controlled conformational switch that allosterically modulates the catalytic activity of eukaryotic IMPDHs. Remarkably, retinopathy-associated mutations lie within the mechanical hinges of the conformational change, highlighting its physiological relevance. Our results expand the mechanistic repertoire of Bateman domains and pave the road to new approaches targeting IMPDHs.