9E0M
CryoEM structure of holoenzyme of inducible Lysine decarboxylase from Hafnia alvei holoenzyme at 2.19 Angstrom resolution
Summary for 9E0M
| Entry DOI | 10.2210/pdb9e0m/pdb |
| Related | 3N75 |
| EMDB information | 47362 |
| Descriptor | Lysine decarboxylase, inducible (2 entities in total) |
| Functional Keywords | l-lysine carboxylyase, ph homeostasis, cadaverine, pyridoxal-phosphate protein, lyase |
| Biological source | Hafnia alvei ATCC 51873 |
| Total number of polymer chains | 10 |
| Total formula weight | 804334.06 |
| Authors | Duhoo, Y.,Desfosses, A.,Gutsche, I.,Doukov, T.I.,Berkowitz, D.B. (deposition date: 2024-10-18, release date: 2025-06-04) |
| Primary citation | Baine, J.M.,Duhoo, Y.,Doukov, T.,Desfosses, A.,Bisello, G.,Beio, M.L.,Bauer, O.,Perduca, M.,Bacia-Verloop, M.,Bertoldi, M.,Phillips, R.S.,Gutsche, I.,Berkowitz, D.B. alpha-Hydrazino Acids Inhibit Pyridoxal Phosphate-Dependent Decarboxylases via "Catalytically Correct" Ketoenamine Tautomers: A Special Motif for Chemical Biology and Drug Discovery? Acs Catalysis, 15:8204-8218, 2025 Cited by PubMed Abstract: We present evidence that supports a 'correct hydrazone tautomer/Dunathan alignment model' for how α-hydrazino analogues of α-amino acids inhibit PLP enzymes. Described is the asymmetric synthesis of l- and d-α-hydrazino acid l-lysine analogues and their inhibition of lysine decarboxylase (LdcI) via kinetic analysis, stopped-flow spectrophotometry, and cryo-EM. We describe a similar investigation of the important anti-Parkinsonism drug, carbidopa, with its human DOPA decarboxylase (hDdc) target. Evidence is consistent with these three hydrazino analogues forming the catalytically relevant ketoenamine PLP-hydrazone tautomer in their target active sites, with the α-carboxylate groups, though insulated, aligning with the PLP-π-system in a Dunathan-model-like orientation. High-resolution cryo-EM structures of the LdcI holoenzyme (pdb 9E0M-2.1Å) and LdcI-bound l- and d-hydrazones (pdb 9E0O-2.0 Å; pdb 9E0Q-2.3Å) and the first X-ray crystal structure of hDdc-bound carbidopa (pdb 9GNS-1.93Å) support this 'correct tautomer' model. These insights are expected to guide future PLP enzyme inhibitor development. PubMed: 40401103DOI: 10.1021/acscatal.5c00326 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (2.2 Å) |
Structure validation
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