PDBsum entry 4xb2

Oxidoreductase

PDB id: 4xb2

Contents

Protein chains

319 a.a.

Ligands

NDP ×2

HSE ×2

Metals

_NA ×2

Waters ×211

PDB id:

4xb2

Name:

Oxidoreductase

Title:

Hyperthermophilic archaeal homoserine dehydrogenase mutant in complex with NADPH

Structure:

319aa long hypothetical homoserine dehydrogenase. Chain: a, b. Engineered: yes. Mutation: yes

Source:

Pyrococcus horikoshii ot3. Organism_taxid: 70601. Strain: ot3. Gene: ph1075. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

2.43Å R-factor: 0.167 R-free: 0.223

Authors:

H.Sakuraba,S.Inoue,K.Yoneda,T.Ohshima

Key ref:

J.Hayashi et al. (2015). Crystal Structures of a Hyperthermophilic Archaeal Homoserine Dehydrogenase Suggest a Novel Cofactor Binding Mode for Oxidoreductases. Sci Rep, 5, 11674. PubMed id: 26154028 DOI: 10.1038/srep11674

Date:

16-Dec-14 Release date: 15-Jul-15

Protein chains

O58802  (O58802_PYRHO) -  homoserine dehydrogenase from Pyrococcus horikoshii (strain ATCC 700860 / DSM 12428 / JCM 9974 / NBRC 100139 / OT-3)

Seq: 319 a.a.

Struc: 319 a.a.*

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

Enzyme reactions

• Enzyme class: E.C.1.1.1.3 - homoserine dehydrogenase.
• Pathway: Threonine Biosynthesis
• Reaction:
  1. L-homoserine + NAD⁺ = L-aspartate 4-semialdehyde + NADH + H⁺
  2. L-homoserine + NADP⁺ = L-aspartate 4-semialdehyde + NADPH + H⁺

L-homoserine (Bound ligand (Het Group name = HSE) corresponds exactly) + NAD(+) (Bound ligand (Het Group name = NDP) matches with 91.67% similarity) = L-aspartate 4-semialdehyde + NADH + H(+)

L-homoserine (Bound ligand (Het Group name = HSE) corresponds exactly) + NADP(+) (Bound ligand (Het Group name = NDP) corresponds exactly) = L-aspartate 4-semialdehyde + NADPH + H(+)

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

reference

DOI no: 10.1038/srep11674

Sci Rep 5:11674 (2015)

PubMed id: 26154028

Crystal Structures of a Hyperthermophilic Archaeal Homoserine Dehydrogenase Suggest a Novel Cofactor Binding Mode for Oxidoreductases.

J.Hayashi, S.Inoue, K.Kim, K.Yoneda, Y.Kawarabayasi, T.Ohshima, H.Sakuraba.

ABSTRACT

NAD(P)-dependent dehydrogenases differ according to their coenzyme preference: some prefer NAD, others NADP, and still others exhibit dual cofactor specificity. The structure of a newly identified archaeal homoserine dehydrogenase showed this enzyme to have a strong preference for NADP. However, NADP did not act as a cofactor with this enzyme, but as a strong inhibitor of NAD-dependent homoserine oxidation. Structural analysis and site-directed mutagenesis showed that the large number of interactions between the cofactor and the enzyme are responsible for the lack of reactivity of the enzyme towards NADP. This observation suggests this enzyme exhibits a new variation on cofactor binding to a dehydrogenase: very strong NADP binding that acts as an obstacle to NAD(P)-dependent dehydrogenase catalytic activity.