July 7, 2022

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Catalytic reaction mechanism of non-heme ferrous dioxygenase (NicX)

Catalytic reaction mechanism of non-heme ferrous dioxygenase (NicX)

 

Catalytic reaction mechanism of non-heme ferrous dioxygenase (NicX).  Significant progress has been made in the study of the catalytic reaction mechanism of non-heme ferrous dioxygenase (NicX).

Catalytic reaction mechanism of non-heme ferrous dioxygenase (NicX)

Recently, Professor Tang Hongzhi and Professor Zhao Yilei from the School of Life Science and Technology of Shanghai Jiaotong University and the Microbial Catabolism Team of the State Key Laboratory of Microbial Metabolism have jointly published an online publication entitled “Structure-guided insights into heterocyclic ring-” in the international authoritative journal “Nature Communications”. The cleavage catalysis of the non-heme Fe (II) dioxygenase NicX” research paper reveals the catalytic reaction mechanism of the non-heme Fe (II) dioxygenase NicX.

2,5-Hydroxypyridine (DHP) is a metabolic intermediate in the catabolism of many pyridine derivatives, which can cause DNA strand breaks and is a potential carcinogen, which can be catalyzed by dioxygenase (NicX) to open the ring It is N-formyl maleic acid (NFM). The enzymes that catalyze the benzene ring-opening reaction have been thoroughly studied in terms of structure and mechanism. However, there are few reports on the enzymes that catalyze the pyridine ring-opening reaction and the catalytic reaction mechanism.

This study analyzed the structure of the NicX monomer and the complex structure of NicX with the small molecule substrate DHP and the product NFM. The crystal structure shows that NicX uses His265, Ser302, His318 and Asp320 to coordinate metal ferrous ions.

The non-heme ferrous dioxygenase structural protein with Ser as the ferrous ion ligand is also the first report. If these four Mutations in residues will make the enzyme lose its ability to bind ferrous metal ions.

Comparing the structure of the resting enzyme with the enzyme-binding substrate and the enzyme-binding product, it is found that the amino acid residue Leu104-His105 plays a role in binding and stabilizing the substrate during the catalytic reaction process, and the conformational change will close the channel II , And open a hydrophobic channel to the active center at the same time.

Further combined with QM/MM calculation and analysis, the catalytic mechanism of oxygen binding to the top position is proposed: oxygen is bound between the substrate and ferrous ions, and the NH on the substrate pyridine ring participates in proton transfer to activate oxygen molecules, prompting oxygen to attack the substrate. ,

Then the OO bond is broken and one of the oxygen atoms is inserted into the pyridine ring to form a seven-membered ring intermediate, and the subsequent seven-membered ring is opened to produce the product.

 

 

 

 

(source:internet, reference only)


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