PDBsum entry 4mlr

Lyase

PDB id: 4mlr

Contents

Protein chains

(+ 2 more) 296 a.a.

Ligands

LYS ×8

EDO ×9

ACT ×2

PG4 ×2

PGE ×5

GOL

Waters ×202

PDB id:

4mlr

Name:

Lyase

Title:

Dihydrodipicolinate synthase from c. Jejuni, y110f mutation with pyruvate and lysine

Structure:

Dihydrodipicolinate synthase. Chain: a, b, c, d, e, f, g, h. Synonym: htpa synthase, 4-hydroxy-tetrahydrodipicolinate synthase. Engineered: yes. Mutation: yes

Source:

Campylobacter jejuni. Organism_taxid: 197. Gene: dapa. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

2.20Å R-factor: 0.217 R-free: 0.269

Authors:

C.J.T.Conly

Key ref:

C.J.Conly et al. (2014). Tyrosine 110 plays a critical role in regulating the allosteric inhibition of Campylobacter jejuni dihydrodipicolinate synthase by lysine. Biochemistry, 53, 7396-7406. PubMed id: 25369463 DOI: 10.1021/bi5012157

Date:

06-Sep-13 Release date: 14-Jan-15

Protein chains

Q9PPB4  (DAPA_CAMJE) -  4-hydroxy-tetrahydrodipicolinate synthase from Campylobacter jejuni subsp. jejuni serotype O:2 (strain ATCC 700819 / NCTC 11168)

Seq: 298 a.a.

Struc: 296 a.a.*

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

Enzyme reactions

• Enzyme class: E.C.4.3.3.7 - 4-hydroxy-tetrahydrodipicolinate synthase.
• Reaction: L-aspartate 4-semialdehyde + pyruvate = (2S,4S)-4-hydroxy-2,3,4,5- tetrahydrodipicolinate + H2O + H⁺

L-aspartate 4-semialdehyde (Bound ligand (Het Group name = LYS) matches with 63.64% similarity) + pyruvate = (2S,4S)-4-hydroxy-2,3,4,5- tetrahydrodipicolinate + H2O + H(+)

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

Added reference

DOI no: 10.1021/bi5012157

Biochemistry 53:7396-7406 (2014)

PubMed id: 25369463

Tyrosine 110 plays a critical role in regulating the allosteric inhibition of Campylobacter jejuni dihydrodipicolinate synthase by lysine.

C.J.Conly, Y.V.Skovpen, S.Li, D.R.Palmer, D.A.Sanders.

ABSTRACT

Dihydrodipicolinate synthase (DHDPS), an enzyme found in most bacteria and plants, controls a critical step in the biosynthesis of l-lysine and meso-diaminopimelate, necessary components for bacterial cell wall biosynthesis. DHDPS catalyzes the condensation of pyruvate and (S)-aspartate-β-semialdehyde, forming an unstable product that is dehydrated to dihydrodipicolinate. The tetrameric enzyme is allosterically inhibited by l-lysine, and a better understanding of the allosteric inhibition mechanism is necessary for the design of potent antibacterial therapeutics. Here we describe the high-resolution crystal structures of DHDPS from Campylobacter jejuni with and without its inhibitor bound to the allosteric sites. These structures reveal a role for Y110 in the regulation of the allosteric inhibition by lysine. Mutation of Y110 to phenylalanine results in insensitivity to lysine inhibition, although the mutant crystal structure reveals that lysine does bind in the allosteric site. Comparison of the lysine-bound Y110F structure with wild-type structures reveals that key structural changes due to lysine binding are absent in this mutant.