6N2H

Structure of D-ornithine/D-lysine decarboxylase from Salmonella typhimurium

Summary for 6N2H

• Entry DOI: 10.2210/pdb6n2h/pdb
• Descriptor: D-ornithine/D-lysine decarboxylase, DIMETHYL SULFOXIDE, 1,4-DIETHYLENE DIOXIDE, ... (4 entities in total)
• Functional Keywords: pyridoxal-5'-phosphate, fold iii, decarboxylase, d-amino acid, lyase
• Biological source: Salmonella typhimurium
• Total number of polymer chains: 1
• Total formula weight: 54976.00

Authors

Phillips, R.S.,Hoover, T.R. (deposition date: 2018-11-13, release date: 2019-10-23, Last modification date: 2023-11-15)

Primary citation

Phillips, R.S.,Poteh, P.,Krajcovic, D.,Miller, K.A.,Hoover, T.R.
Crystal Structure of d-Ornithine/d-Lysine Decarboxylase, a Stereoinverting Decarboxylase: Implications for Substrate Specificity and Stereospecificity of Fold III Decarboxylases.
Biochemistry, 58:1038-1042, 2019

PubMed Abstract: A newly discovered Fold III pyridoxal 5'-phosphate (PLP)-dependent decarboxylase, d-ornithine/lysine decarboxylase (DOKDC), catalyzes decarboxylation of d-lysine and d-ornithine with inversion of stereochemistry. The X-ray crystal structure of DOKDC has been determined to 1.72 Å. DOKDC has a low level of sequence identity (<30%) with meso-diaminopimelate decarboxylase (DAPDC) and l-lysine/ornithine decarboxylase (LODC), but its three-dimensional structure is very similar. The distal binding site of DAPDC contains a conserved arginine that forms an ion pair with the l-carboxylate end of DAP. In both LODC and DOKDC, this distal site is modified by replacement of the arginine with aspartate, changing the substrate specificity. l-Ornithine decarboxylase (ODC) and LODC have a conserved phenylalanine on the re-face of the PLP complex that has been found to play a key role in the decarboxylation mechanism. We have found that both DAPDC and DOKDC have tyrosine instead of phenylalanine at this position, which precludes the binding of l-amino acids. Because the PLP-binding lysine in ODC, LODC, DAPDC, and DOKDC is located on the re-face of the PLP, we propose that this is the acid group responsible for protonation of the product, thus resulting in the observed retention of configuration for decarboxylation of l-amino acids and inversion for decarboxylation of d-amino acids. The reactions of DAPDC and DOKDC are likely accelerated by positive electrostatics on the re-face by the lysine ε-ammonium ion and on the si-face by closure of the lid over the active site, resulting in desolvation and destabilization of the d-amino acid carboxylate.

PubMed: 30699288
DOI: 10.1021/acs.biochem.8b01319

Experimental method

X-RAY DIFFRACTION (1.72 Å)