PDBsum entry: 1ibt

Lyase

PDB id: 1ibt

Contents

Protein chains

81 a.a. *

229 a.a. *

76 a.a. *

Waters ×53

* Residue conservation analysis

PDB id:

1ibt

Name:

Lyase

Title:

Structure of the d53,54n mutant of histidine decarboxylase a

Structure:

Histidine decarboxylase beta chain. Chain: a, c, e. Fragment: beta chain (residues 1-81). Synonym: pi chain. Engineered: yes. Mutation: yes. Histidine decarboxylase alpha chain. Chain: b, d, f. Fragment: alpha chain (residues 82-310).

Source:

Lactobacillus sp.. Organism_taxid: 1593. Strain: 30a. Gene: hdca. Expressed in: escherichia coli. Expression_system_taxid: 562. Expression_system_taxid: 562

Biol. unit:

Dodecamer (from PDB file)

Resolution:

2.60Å R-factor: 0.260 R-free: 0.316

Authors:

S.Worley,E.Schelp,A.F.Monzingo,S.Ernst,J.D.Robertus

Key ref:

S.Worley et al. (2002). Structure and cooperativity of a T-state mutant of histidine decarboxylase from Lactobacillus 30a. Proteins, 46, 321-329. PubMed id: 11835507 DOI: 10.1002/prot.10042

Date:

29-Mar-01 Release date: 13-Mar-02

Protein chains

P00862  (DCHS_LACS3) -  Histidine decarboxylase proenzyme

Seq: 311 a.a.

Struc: 81 a.a.*

Protein chains

P00862  (DCHS_LACS3) -  Histidine decarboxylase proenzyme

Seq: 311 a.a.

Struc: 229 a.a.*

Protein chain

P00862  (DCHS_LACS3) -  Histidine decarboxylase proenzyme

Seq: 311 a.a.

Struc: 76 a.a.

* PDB and UniProt seqs differ at 3 residue positions (black crosses)

Enzyme reactions

• Enzyme class: Chains A, B, C, D, E, F: E.C.4.1.1.22 - Histidine decarboxylase.
• Reaction: L-histidine = histamine + CO₂
• Cofactor: Pyruvate or pyridoxal 5'-phosphate

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

 Gene Ontology (GO) functional annotation 

• Biological process: cellular amino acid metabolic process (2 terms)
• Biochemical function: carboxy-lyase activity (2 terms)

reference

DOI no: 10.1002/prot.10042

Proteins 46:321-329 (2002)

PubMed id: 11835507

Structure and cooperativity of a T-state mutant of histidine decarboxylase from Lactobacillus 30a.

S.Worley, E.Schelp, A.F.Monzingo, S.Ernst, J.D.Robertus.

ABSTRACT

Histidine decarboxylase (HDC) from Lactobacillus 30a converts histidine to histamine, a process that enables the bacteria to maintain the optimum pH range for cell growth. HDC is regulated by pH; it is active at low pH and inactive at neutral to alkaline pH. The X-ray structure of HDC at pH 8 revealed that a helix was disordered, resulting in the disruption of the substrate-binding site. The HDC trimer has also been shown to exhibit cooperative kinetics at neutral pH, that is, histidine can trigger a T-state to R-state transition. The D53,54N mutant of HDC has an elevated Km, even at low pH, indicating that the enzyme assumes the low activity T-state. We have solved the structures of the D53,54N mutant at low pH, with and without the substrate analog histidine methyl ester (HME) bound. Structural analysis shows that the apo-D53,54N mutant is in the inactive or T-state and that binding of the substrate analog induces the enzyme to adopt the active or R-state. A mechanism for the cooperative transition is proposed.

Selected figure(s)

Figure 2.
Figure 2. Binding of HME in the active site of the D53,54N mutant of HDC. Residues from the right-hand monomer of the molecular interface are labeled with ( ). The pyruvoyl moiety (PVL) is part of the left-hand monomer and is shown bonded to HME. Hydrogen bonds are drawn with dashed lines.

Figure 4.
Figure 4. Superposition of the wild-type pH 8 (T-state) and pH 4.8 (R-state) models at the molecular interface shows how the change in the position of residue E227 affects its interaction with R64 . The pH 8 model is shown with light bonds and pH 4.8 model with dark bonds. In the R-state model, E227 forms ion pair interactions across the molecular interface with R48 and R64 . R64 also forms an interaction with D231. In the T state, interactions with E227 are not observed. R64 only interacts with D231, and R48 is disordered.

The above figures are reprinted by permission from John Wiley & Sons, Inc.: Proteins (2002, 46, 321-329) copyright 2002.

Figures were selected by the author.