1M6H

Human glutathione-dependent formaldehyde dehydrogenase

Summary for 1M6H

• Entry DOI: 10.2210/pdb1m6h/pdb
• Related: 1M6W 1MA0
• Descriptor: Glutathione-dependent formaldehyde dehydrogenase, ZINC ION, POTASSIUM ION, ... (5 entities in total)
• Functional Keywords: glutathione-dependent formaldehyde dehydrogenase class iii alcohol dehydrogenase, oxidoreductase
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm: P11766
• Total number of polymer chains: 2
• Total formula weight: 80096.69

Authors

Sanghani, P.C.,Robinson, H.,Bosron, W.F.,Hurley, T.D. (deposition date: 2002-07-16, release date: 2002-07-26, Last modification date: 2024-02-14)

Primary citation

Sanghani, P.C.,Robinson, H.,Bosron, W.F.,Hurley, T.D.
Human glutathione-dependent formaldehyde dehydrogenase. Structures of apo, binary, and inhibitory ternary complexes.
Biochemistry, 41:10778-10786, 2002

PubMed Abstract: The human glutathione-dependent formaldehyde dehydrogenase is unique among the structurally studied members of the alcohol dehydrogenase family in that it follows a random bi bi kinetic mechanism. The structures of an apo form of the enzyme, a binary complex with substrate 12-hydroxydodecanoic acid, and a ternary complex with NAD+ and the inhibitor dodecanoic acid were determined at 2.0, 2.3, and 2.3 A resolution by X-ray crystallography using the anomalous diffraction signal of zinc. The structures of the enzyme and its binary complex with the primary alcohol substrate, 12-hydroxydodecanoic acid, and the previously reported binary complex with the coenzyme show that the binding of the first substrate (alcohol or coenzyme) causes only minor changes to the overall structure of the enzyme. This is consistent with the random mechanism of the enzyme where either of the substrates binds to the free enzyme. The catalytic-domain position in these structures is intermediate to the "closed" and "open" conformations observed in class I alcohol dehydrogenases. More importantly, two different tetrahedral coordination environments of the active site zinc are observed in these structures. In the apoenzyme, the active site zinc is coordinated to Cys44, His66 and Cys173, and a water molecule. In the inhibitor complex, the coordination environment involves Glu67 instead of the solvent water molecule. The coordination environment involving Glu67 as the fourth ligand likely represents an intermediate step during ligand exchange at the active site zinc. These observations provide new insight into metal-assisted catalysis and substrate binding in glutathione-dependent formaldehyde dehydrogenase.

PubMed: 12196016
DOI: 10.1021/bi0257639

Experimental method

X-RAY DIFFRACTION (2 Å)