PDBsum entry 6a0r

Oxidoreductase

PDB id: 6a0r

Contents

Protein chains

331 a.a.

Ligands

FMT ×17

CXS ×2

GOL ×2

UNL

Metals

_NA ×2

Waters ×787

PDB id:

6a0r

Name:

Oxidoreductase

Title:

Homoserine dehydrogenase from thermus thermophilus hb8 unliganded form

Structure:

Homoserine dehydrogenase. Chain: b, a. Engineered: yes

Source:

Thermus thermophilus hb8. Organism_taxid: 300852. Strain: hb8. Gene: ttha0489. Expressed in: escherichia coli. Expression_system_taxid: 562

Resolution:

1.83Å R-factor: 0.150 R-free: 0.177

Authors:

S.Akai,H.Ikushiro,T.Sawai,T.Yano,N.Kamiya,I.Miyahara

Key ref:

S.Akai et al. (2019). The crystal structure of homoserine dehydrogenase complexed with l-homoserine and NADPH in a closed form. J Biochem, 165, 185-195. PubMed id: 30423116 DOI: 10.1093/jb/mvy094

Date:

06-Jun-18 Release date: 28-Nov-18

Protein chains

Q5SL04  (Q5SL04_THET8) -  Homoserine dehydrogenase from Thermus thermophilus (strain ATCC 27634 / DSM 579 / HB8)

Seq: 332 a.a.

Struc: 331 a.a.

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 = UNL) matches with 40.00% similarity) + NAD(+) = L-aspartate 4-semialdehyde + NADH + H(+)

L-homoserine (Bound ligand (Het Group name = UNL) matches with 40.00% similarity) + NADP(+) = L-aspartate 4-semialdehyde + NADPH + H(+)

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

reference

DOI no: 10.1093/jb/mvy094

J Biochem 165:185-195 (2019)

PubMed id: 30423116

The crystal structure of homoserine dehydrogenase complexed with l-homoserine and NADPH in a closed form.

S.Akai, H.Ikushiro, T.Sawai, T.Yano, N.Kamiya, I.Miyahara.

ABSTRACT

Homoserine dehydrogenase from Thermus thermophilus (TtHSD) is a key enzyme in the aspartate pathway that catalyses the reversible conversion of l-aspartate-β-semialdehyde to l-homoserine (l-Hse) with NAD(P)H. We determined the crystal structures of unliganded TtHSD, TtHSD complexed with l-Hse and NADPH, and Lys99Ala and Lys195Ala mutant TtHSDs, which have no enzymatic activity, complexed with l-Hse and NADP+ at 1.83, 2.00, 1.87 and 1.93 Å resolutions, respectively. Binding of l-Hse and NADPH induced the conformational changes of TtHSD from an open to a closed form: the mobile loop containing Glu180 approached to fix l-Hse and NADPH, and both Lys99 and Lys195 could make hydrogen bonds with the hydroxy group of l-Hse. The ternary complex of TtHSDs in the closed form mimicked a Michaelis complex better than the previously reported open form structures from other species. In the crystal structure of Lys99Ala TtHSD, the productive geometry of the ternary complex was almost preserved with one new water molecule taking over the hydrogen bonds associated with Lys99, while the positions of Lys195 and l-Hse were significantly retained with those of the wild-type enzyme. These results propose new possibilities that Lys99 is the acid-base catalytic residue of HSDs.