PDBsum entry 1m6h

Oxidoreductase

PDB id: 1m6h

Contents

Protein chain

373 a.a. *

Ligands

PO4 ×5

Metals

_ZN ×4

__K ×2

Waters ×895

* Residue conservation analysis

PDB id:

1m6h

Name:

Oxidoreductase

Title:

Human glutathione-dependent formaldehyde dehydrogenase

Structure:

Glutathione-dependent formaldehyde dehydrogenase. Chain: a, b. Synonym: alcohol dehydrogenase class iii chi chain. Alcohol dehydrogenase (class iii), chi polypeptide. Fdh. E.C.1.2.1.1. Engineered: yes. Other_details: apoenzyme

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: adh5. Expressed in: escherichia coli. Expression_system_taxid: 562.

Biol. unit:

Dimer (from PQS)

Resolution:

2.00Å R-factor: 0.185 R-free: 0.218

Authors:

P.C.Sanghani,H.Robinson,W.F.Bosron,T.D.Hurley

Key ref:

P.C.Sanghani et al. (2002). Human glutathione-dependent formaldehyde dehydrogenase. Structures of apo, binary, and inhibitory ternary complexes. Biochemistry, 41, 10778-10786. PubMed id: 12196016 DOI: 10.1021/bi0257639

Date:

16-Jul-02 Release date: 26-Jul-02

Protein chains

P11766  (ADHX_HUMAN) -  Alcohol dehydrogenase class-3 from Homo sapiens

Seq: 374 a.a.

Struc: 373 a.a.

Enzyme reactions

• Enzyme class 1: E.C.1.1.1.- - ?????
• Enzyme class 2: E.C.1.1.1.1 - alcohol dehydrogenase.
• Reaction:
  1. a primary alcohol + NAD⁺ = an aldehyde + NADH + H⁺
  2. a secondary alcohol + NAD⁺ = a ketone + NADH + H⁺
• Cofactor: Zn(2+) or Fe cation
• Enzyme class 3: E.C.1.1.1.284 - S-(hydroxymethyl)glutathione dehydrogenase.
• Reaction:
  1. S-(hydroxymethyl)glutathione + NADP⁺ = S-formylglutathione + NADPH + H⁺
  2. S-(hydroxymethyl)glutathione + NAD⁺ = S-formylglutathione + NADH + H⁺

Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

DOI no: 10.1021/bi0257639

Biochemistry 41:10778-10786 (2002)

PubMed id: 12196016

Human glutathione-dependent formaldehyde dehydrogenase. Structures of apo, binary, and inhibitory ternary complexes.

P.C.Sanghani, H.Robinson, W.F.Bosron, T.D.Hurley.

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.