PDBsum entry 4xtd

Oxidoreductase

PDB id: 4xtd

Contents

Protein chains

377 a.a.

Ligands

IMP ×2

Waters ×134

PDB id:

4xtd

Name:

Oxidoreductase

Title:

Structure of the covalent intermediate e-xmp Of the imp dehydrogenase of ashbya gossypii

Structure:

Inosine-5'-monophosphate dehydrogenase,inosine-5'- monophosphate dehydrogenase. Chain: a, b. Synonym: impdh,impdh. Engineered: yes. Mutation: yes. Other_details: the covalent intermediate impdh-xmp Bound to cys334 in the active site and non-covalently bound imp are present at around 50% in the crystal.

Source:

Ashbya gossypii (strain atcc 10895 / cbs 109.51 / fgsc 9923 / nrrl y-1056). Yeast. Organism_taxid: 284811. Gene: agos_aer117w. Expressed in: escherichia coli. Expression_system_taxid: 562

Resolution:

2.05Å R-factor: 0.185 R-free: 0.214

Authors:

R.M.Buey,R.Ledesma-Amaro,M.Balsera,J.M.De Pereda,J.L.Revuelta

Key ref:

R.M.Buey et al. (2015). Increased riboflavin production by manipulation of inosine 5'-monophosphate dehydrogenase in Ashbya gossypii. Appl Microbiol Biotechnol, 99, 9577-9589. PubMed id: 26150243 DOI: 10.1007/s00253-015-6710-2

Date:

23-Jan-15 Release date: 22-Jul-15

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: 377 a.a.

Enzyme reactions

• Enzyme class: 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 = IMP) corresponds exactly) + H2O = XMP + NADH + H(+)

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

reference

DOI no: 10.1007/s00253-015-6710-2

Appl Microbiol Biotechnol 99:9577-9589 (2015)

PubMed id: 26150243

Increased riboflavin production by manipulation of inosine 5'-monophosphate dehydrogenase in Ashbya gossypii.

R.M.Buey, R.Ledesma-Amaro, M.Balsera, J.M.de Pereda, J.L.Revuelta.

ABSTRACT

Guanine nucleotides are the precursors of essential biomolecules including nucleic acids and vitamins such as riboflavin. The enzyme inosine-5'-monophosphate dehydrogenase (IMPDH) catalyzes the ratelimiting step in the guanine nucleotide de novo biosynthetic pathway and plays a key role in controlling the cellular nucleotide pools. Thus, IMPDH is an important metabolic bottleneck in the guanine nucleotide synthesis, susceptible of manipulation by means of metabolic engineering approaches. Herein, we report the functional and structural characterization of the IMPDH enzyme from the industrial fungus Ashbya gossypii. Our data show that the overexpression of the IMPDH gene increases the metabolic flux through the guanine pathway and ultimately enhances 40 % riboflavin production with respect to the wild type. Also, IMPDH disruption results in a 100-fold increase of inosine excretion to the culture media. Our results contribute to the developing metabolic engineering toolbox aiming at improving the production of metabolites with biotechnological interest in A. gossypii.