4pzp
From Proteopedia
Substrate-free structure of D-alanine carrier protein ligase DltA from Bacillus cereus
Structural highlights
FunctionDLTA_BACCR Involved in the biosynthesis of D-alanyl-lipoteichoic acid (LTA). Catalyzes an ATP-dependent two-step reaction where it forms a high energy D-alanyl AMP intermediate and transfers the alanyl residues from AMP to Dcp (By similarity). Publication Abstract from PubMedD-alanylation of the lipoteichoic acid on Gram-positive cell wall is dependent on dlt gene-encoded proteins DltA, DltB, DltC and DltD. The D-alanyl carrier protein ligase DltA, as a remote homolog of acyl-(coenzyme A) (CoA) synthetase, cycles through two active conformations for the catalysis of adenylation and subsequent thiolation of D-alanine (D-Ala). The crystal structure of DltA in the absence of any substrate was observed to have a noticeably more disordered pocket for ATP which would explain why DltA has relatively low affinity for ATP in the absence of any D-alanyl carrier. We have previously enabled the thiolation of D-alanine in the presence of CoA as the mimic of D-alanyl carrier protein DltC which carries a 4'-phosphopantetheine group on a serine residue. Here we show that the resulting Michaelis constants in the presence of saturating CoA for both ATP and D-alanine were reduced more than 10 fold as compared to the values obtained in the absence of CoA. The presence of CoA also made DltA ~100-fold more selective on D-alanine over L-alanine. The CoA-enhanced substrate recognition further implies that the ATP and D-alanine substrates of the adenylation reaction are incorporated when the DltA enzyme cycles through its thiolation conformation. Thiolation-enhanced substrate recognition by D-alanyl carrier protein ligase DltA from Bacillus cereus.,Du L, Luo Y F1000Res. 2014 May 13;3:106. doi: 10.12688/f1000research.4097.1. eCollection, 2014. PMID:25285205[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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