7K35
EQADH-NADH-4-METHYLBENZYL ALCOHOL, p21
Summary for 7K35
| Entry DOI | 10.2210/pdb7k35/pdb |
| Related | 4XD2 5VL0 5VN1 7JQA |
| Descriptor | Alcohol dehydrogenase E chain, ZINC ION, 1,4-DIHYDRONICOTINAMIDE ADENINE DINUCLEOTIDE, ... (6 entities in total) |
| Functional Keywords | alcohol dehydrogenase, nadh, horse liver, oxidoreductase |
| Biological source | Equus caballus (Horse) |
| Total number of polymer chains | 4 |
| Total formula weight | 163323.13 |
| Authors | Plapp, B.V.,Ramaswamy, S. (deposition date: 2020-09-10, release date: 2020-09-23, Last modification date: 2023-10-18) |
| Primary citation | Plapp, B.V.,Subramanian, R. Alternative binding modes in abortive NADH-alcohol complexes of horse liver alcohol dehydrogenase. Arch.Biochem.Biophys., 701:108825-108825, 2021 Cited by PubMed Abstract: Enzymes typically have high specificity for their substrates, but the structures of substrates and products differ, and multiple modes of binding are observed. In this study, high resolution X-ray crystallography of complexes with NADH and alcohols show alternative modes of binding in the active site. Enzyme crystallized with the good substrates NAD and 4-methylbenzyl alcohol was found to be an abortive complex of NADH with 4-methylbenzyl alcohol rotated to a "non-productive" mode as compared to the structures that resemble reactive Michaelis complexes with NAD and 2,2,2-trifluoroethanol or 2,3,4,5,6-pentafluorobenzyl alcohol. The NADH is formed by reduction of the NAD with the alcohol during the crystallization. The same structure was also formed by directly crystallizing the enzyme with NADH and 4-methylbenzyl alcohol. Crystals prepared with NAD and 4-bromobenzyl alcohol also form the abortive complex with NADH. Surprisingly, crystals prepared with NAD and the strong inhibitor 1H,1H-heptafluorobutanol also had NADH, and the alcohol was bound in two different conformations that illustrate binding flexibility. Oxidation of 2-methyl-2,4-pentanediol during the crystallization apparently led to reduction of the NAD. Kinetic studies show that high concentrations of alcohols can bind to the enzyme-NADH complex and activate or inhibit the enzyme. Together with previous studies on complexes with NADH and formamide analogues of the carbonyl substrates, models for the Michaelis complexes with NAD-alcohol and NADH-aldehyde are proposed. PubMed: 33675814DOI: 10.1016/j.abb.2021.108825 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.2 Å) |
Structure validation
Download full validation report
