Crystal Structure of d-Ornithine/d-Lysine Decarboxylase, a Stereoinverting Decarboxylase: Implications for Substrate Specificity and Stereospecificity of Fold III Decarboxylases

Journal Article · Wed Jan 30 00:00:00 EST 2019 · Biochemistry

DOI:https://doi.org/10.1021/acs.biochem.8b01319· OSTI ID:1504969

Phillips, Robert S. ^[1]; Poteh, Pafe ^[1]; Krajcovic, Donovan ^[1]; Miller, Katherine A. ^[2]; Hoover, Timothy R. ^[1]

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1. Univ. of Georgia, Athens, GA (United States)
2. Univ. of Georgia, Athens, GA (United States); Nestle Purina North America, St Louis, MO (United States)

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. Here, 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.

• Research Organization: Argonne National Laboratory (ANL), Argonne, IL (United States)
• Sponsoring Organization: National Inst. of Health; USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22)
• Grant/Contract Number: W-31-109-ENG-3
• OSTI ID: 1504969
• Journal Information: Biochemistry, Journal Name: Biochemistry Journal Issue: 8 Vol. 58; ISSN 0006-2960
• Publisher: American Chemical Society (ACS)
• Country of Publication: United States
• Language: ENGLISH

Related Subjects

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY
59 BASIC BIOLOGICAL SCIENCES
chemical specificity
chemical structure
monomers
organic reactions
peptides and proteins