Any feedback?
Please rate this page
(literature.php)
(0/150)

BRENDA support

Literature summary extracted from

  • Stevens, D.R.; Hammes-Schiffer, S.
    Examining the mechanism of phosphite dehydrogenase with quantum mechanical/molecular mechanical free energy simulations (2020), Biochemistry, 59, 943-954.
    View publication on PubMed

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
1.20.1.1 phosphonate + NAD+ + H2O Stutzerimonas stutzeri
-
 phosphate + NADH + H+
-
 ?

Organism

EC Number Organism UniProt Comment Textmining
1.20.1.1 Stutzerimonas stutzeri O69054 Stutzerimonas stutzeri
-

Reaction

EC Number Reaction Comment Organism Reaction ID
1.20.1.1 phosphonate + NAD+ + H2O = phosphate + NADH + H+ reaction mechanism for enzyme with monoanionic phosphite substrate with proximal water (the monoOA-proximal or monoOB-proximal string), detailed overview. Although the mechanism for the monoanionic phosphite substrate with proximal water is the same when OA or OB is protonated, the free energy barriers and reaction free energies are quite different Stutzerimonas stutzeri
a

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
1.20.1.1 phosphonate + NAD+ + H2O
-
 Stutzerimonas stutzeri phosphate + NADH + H+
-
 ?

Subunits

EC Number Subunits Comment Organism
1.20.1.1 monomer enzyme PTDH is a monomer composed of two domains: the NAD-binding domain, which is the larger of the two domains, and the substrate-binding domain. The two domains are linked through a flexible hinge region. The active site includes the ligand, which is NAD+, the substrate, which is phosphite, the hypothesized general base, His292, and the adjacent residues Arg237, Glu266, Met53, Gly77, and Arg301 Stutzerimonas stutzeri

Synonyms

EC Number Synonyms Comment Organism
1.20.1.1 phosphite dehydrogenase
-
 Stutzerimonas stutzeri
1.20.1.1 PTDH
-
 Stutzerimonas stutzeri

Cofactor

EC Number Cofactor Comment Organism Structure
1.20.1.1 NAD+
-
 Stutzerimonas stutzeri

General Information

EC Number General Information Comment Organism
1.20.1.1 additional information quantum mechanical/molecular mechanical free energy simulations (with the structure of thermostable PTDH with sulfite as the substrate mimic (PDB ID 4E5K) as the starting structure for our simulations) are used for analysis of the enzyme's reaction mechanism. The overall mechanism of PTDH is proposed to involve hydride transfer from phosphite to NAD+, nucleophilic attack on the phosphorus by a water molecule, and proton transfer from the water molecule to the hypothesized base, His292. The finite temperature string method with umbrella sampling is used to generate the free energy surfaces and determine the minimum free energy paths for six different initial conditions that vary in the protonation state of the substrate and the position of the nucleophilic water molecule. Enzyme PTDH is a monomer composed of two domains: the NAD-binding domain, which is the larger of the two domains, and the substrate-binding domain. The two domains are linked through a flexible hinge region. The active site includes the ligand, which is NAD+, the substrate, which is phosphite, the hypothesized general base, His292, and the adjacent residues Arg237, Glu266, Met53, Gly77, and Arg301. Residue Arg237 can also serve as this base if it is deprotonated and His292 is protonated prior to the main chemical transformation, although this scenario is less probable. The phosphite substrate is monoanionic in its active form and that the most likely product is dihydrogen phosphate Stutzerimonas stutzeri
1.20.1.1 physiological function the enzyme phosphite dehydrogenase (PTDH) allows microorganisms such as Pseudomonas stutzeri to thrive in an environment with phosphite as the only source of phosphorus. This enzyme oxidizes phosphite to phosphate in conjunction with the reduction of NAD+ to NADH. PTDH plays a key role in cofactor recycling bioprocesses that utilize NAD+ as a hydride acceptor to regenerate NADH Stutzerimonas stutzeri