PDBsum entry 5nqb

Oxidoreductase

PDB id: 5nqb

Contents

Protein chains

331 a.a.

Ligands

MLI ×7

Waters ×1406

PDB id:

5nqb

Name:

Oxidoreductase

Title:

Rabbit muscle l-lactate dehydrogenase in complex with malonate

Structure:

L-lactate dehydrogenase a chain. Chain: a, b, c, d. Synonym: ldh-a,ldh muscle subunit,ldh-m. Engineered: yes. Mutation: yes

Source:

Oryctolagus cuniculus. Rabbit. Organism_taxid: 9986. Gene: ldha. Expressed in: escherichia coli. Expression_system_taxid: 562

Resolution:

1.58Å R-factor: 0.194 R-free: 0.218

Authors:

B.F.Luisi,V.Olin-Sandoval

Key ref:

M.T.Alam et al. (2017). The self-inhibitory nature of metabolic networks and its alleviation through compartmentalization. Nat Commun, 8, 16018. PubMed id: 28691704

Date:

19-Apr-17 Release date: 03-May-17

Protein chains

P13491  (LDHA_RABIT) -  L-lactate dehydrogenase A chain from Oryctolagus cuniculus

Seq: 332 a.a.

Struc: 331 a.a.*

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

Enzyme reactions

• Enzyme class: E.C.1.1.1.27 - L-lactate dehydrogenase.
• Reaction: (S)-lactate + NAD⁺ = pyruvate + NADH + H⁺

(S)-lactate (Bound ligand (Het Group name = MLI) matches with 62.50% similarity) + NAD(+) = pyruvate + NADH + H(+)

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

reference

Nat Commun 8:16018 (2017)

PubMed id: 28691704

The self-inhibitory nature of metabolic networks and its alleviation through compartmentalization.

M.T.Alam, V.Olin-Sandoval, A.Stincone, M.A.Keller, A.Zelezniak, B.F.Luisi, M.Ralser.

ABSTRACT

Metabolites can inhibit the enzymes that generate them. To explore the general nature of metabolic self-inhibition, we surveyed enzymological data accrued from a century of experimentation and generated a genome-scale enzyme-inhibition network. Enzyme inhibition is often driven by essential metabolites, affects the majority of biochemical processes, and is executed by a structured network whose topological organization is reflecting chemical similarities that exist between metabolites. Most inhibitory interactions are competitive, emerge in the close neighbourhood of the inhibited enzymes, and result from structural similarities between substrate and inhibitors. Structural constraints also explain one-third of allosteric inhibitors, a finding rationalized by crystallographic analysis of allosterically inhibited L-lactate dehydrogenase. Our findings suggest that the primary cause of metabolic enzyme inhibition is not the evolution of regulatory metabolite-enzyme interactions, but a finite structural diversity prevalent within the metabolome. In eukaryotes, compartmentalization minimizes inevitable enzyme inhibition and alleviates constraints that self-inhibition places on metabolism.