PDBsum entry 3fcc

Ligase

PDB id: 3fcc

Contents

Protein chain

500 a.a. *

Ligands

ATP

Metals

_MG

Waters ×133

* Residue conservation analysis

PDB id:

3fcc

Name:

Ligase

Title:

Crystal structure of dlta protein in complex with atp and magnesium

Structure:

D-alanine--poly(phosphoribitol) ligase subunit 1. Chain: a. Synonym: d-alanine-activating enzyme, dae, d-alanine-d-alanyl carrier protein ligase, dcl. Engineered: yes

Source:

Bacillus cereus. Organism_taxid: 226900. Strain: atcc 14579. Gene: bc_1372, dlta. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

2.32Å R-factor: 0.241 R-free: 0.286

Authors:

K.T.Osman,L.Du,Y.He,Y.Luo

Key ref:

K.T.Osman et al. (2009). Crystal structure of Bacillus cereus D-alanyl carrier protein ligase (DltA) in complex with ATP. J Mol Biol, 388, 345-355. PubMed id: 19324056 DOI: 10.1016/j.jmb.2009.03.040

Date:

21-Nov-08 Release date: 14-Apr-09

Protein chain

Q81G39  (DLTA_BACCR) -  D-alanine--D-alanyl carrier protein ligase from Bacillus cereus (strain ATCC 14579 / DSM 31 / CCUG 7414 / JCM 2152 / NBRC 15305 / NCIMB 9373 / NCTC 2599 / NRRL B-3711)

Seq: 504 a.a.

Struc: 500 a.a.

Enzyme reactions

• Enzyme class: E.C.6.2.1.54 - D-alanine--[D-alanyl-carrier protein] ligase.
• Reaction: holo-[D-alanyl-carrier protein] + D-alanine + ATP = D-alanyl-[D-alanyl- carrier protein] + AMP + diphosphate

holo-[D-alanyl-carrier protein] (Bound ligand (Het Group name = ATP) corresponds exactly) + D-alanine + ATP = D-alanyl-[D-alanyl- carrier protein] + AMP + diphosphate

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

reference

DOI no: 10.1016/j.jmb.2009.03.040

J Mol Biol 388:345-355 (2009)

PubMed id: 19324056

Crystal structure of Bacillus cereus D-alanyl carrier protein ligase (DltA) in complex with ATP.

K.T.Osman, L.Du, Y.He, Y.Luo.

ABSTRACT

D-alanylation of lipoteichoic acids modulates the surface charge and ligand binding of the Gram-positive cell wall. Disruption of the bacterial dlt operon involved in teichoic acid alanylation, as well as inhibition of the DltA (D-alanyl carrier protein ligase) protein, has been shown to render the bacterium more susceptible to conventional antibiotics and host defense responses. The DltA catalyzes the adenylation and thiolation reactions of d-alanine. This enzyme belongs to a superfamily of AMP-forming domains such as the ubiquitous acetyl-coenzyme A synthetase. We have determined the 1.9-A-resolution crystal structure of a DltA protein from Bacillus cereus in complex with ATP. This structure sheds light on the geometry of the bound ATP. The invariant catalytic residue Lys492 appears to be mobile, suggesting a molecular mechanism of catalysis for this superfamily of enzymes. Specific roles are also revealed for two other invariant residues: the divalent cation-stabilizing Glu298 and the beta-phosphate-interacting Arg397. Mutant proteins with a glutamine substitution at position 298 or 397 are inactive.

Selected figure(s)

Figure 3.
Fig. 3. Structural comparison of DltA and human medium-chain ACS in stereo. The superimposed ATP-binding pockets are shown. The BcDltA model is shown as in Fig. 2c. The counterparts in the human ACS are shown in gray.

Figure 5.
Fig. 5. Adenylation model in stereo. The model was based on the BcDltA/ATP structure and the BcDltA/adenylate structure. The orientation and coloring scheme are similar to those in Fig. 2b. The epsilon -amino group of the mobile Lys492 residue escorts the electron transfer from the nucleophilic d-alanyl carboxylate group via a pentavalent transition state to the leaving pyrophosphate.

The above figures are reprinted by permission from Elsevier: J Mol Biol (2009, 388, 345-355) copyright 2009.

Figures were selected by the author.

Author's comment

The mobile Lysine appears to be critical in escorting the developing negative charge along the reaction pathway.