6vib

Observing a ring-cleaving dioxygenase in action through a crystalline lens - enol tautomers of ACMS bidentately bound structureObserving a ring-cleaving dioxygenase in action through a crystalline lens - enol tautomers of ACMS bidentately bound structure

Structural highlights

6vib is a 1 chain structure with sequence from Cupriavidus metallidurans CH34. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.84Å
Ligands:	, ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

3HAO_CUPMC Catalyzes the oxidative ring opening of 3-hydroxyanthranilate to 2-amino-3-carboxymuconate semialdehyde, which spontaneously cyclizes to quinolinate.[HAMAP-Rule:MF_00825]^[1]

Publication Abstract from PubMed

The synthesis of quinolinic acid from tryptophan is a critical step in the de novo biosynthesis of nicotinamide adenine dinucleotide (NAD(+)) in mammals. Herein, the nonheme iron-based 3-hydroxyanthranilate-3,4-dioxygenase responsible for quinolinic acid production was studied by performing time-resolved in crystallo reactions monitored by UV-vis microspectroscopy, electron paramagnetic resonance (EPR) spectroscopy, and X-ray crystallography. Seven catalytic intermediates were kinetically and structurally resolved in the crystalline state, and each accompanies protein conformational changes at the active site. Among them, a monooxygenated, seven-membered lactone intermediate as a monodentate ligand of the iron center at 1.59-A resolution was captured, which presumably corresponds to a substrate-based radical species observed by EPR using a slurry of small-sized single crystals. Other structural snapshots determined at around 2.0-A resolution include monodentate and subsequently bidentate coordinated substrate, superoxo, alkylperoxo, and two metal-bound enol tautomers of the unstable dioxygenase product. These results reveal a detailed stepwise O-atom transfer dioxygenase mechanism along with potential isomerization activity that fine-tunes product profiling and affects the production of quinolinic acid at a junction of the metabolic pathway.

Observing 3-hydroxyanthranilate-3,4-dioxygenase in action through a crystalline lens.,Wang Y, Liu KF, Yang Y, Davis I, Liu A Proc Natl Acad Sci U S A. 2020 Jul 30. pii: 2005327117. doi:, 10.1073/pnas.2005327117. PMID:32732435^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Colabroy KL, Zhai H, Li T, Ge Y, Zhang Y, Liu A, Ealick SE, McLafferty FW, Begley TP. The mechanism of inactivation of 3-hydroxyanthranilate-3,4-dioxygenase by 4-chloro-3-hydroxyanthranilate. Biochemistry. 2005 May 31;44(21):7623-31. PMID:15909977 doi:http://dx.doi.org/10.1021/bi0473455
↑ Wang Y, Liu KF, Yang Y, Davis I, Liu A. Observing 3-hydroxyanthranilate-3,4-dioxygenase in action through a crystalline lens. Proc Natl Acad Sci U S A. 2020 Jul 30. pii: 2005327117. doi:, 10.1073/pnas.2005327117. PMID:32732435 doi:http://dx.doi.org/10.1073/pnas.2005327117

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] Colabroy KL, Zhai H, Li T, Ge Y, Zhang Y, Liu A, Ealick SE, McLafferty FW, Begley TP. The mechanism of inactivation of 3-hydroxyanthranilate-3,4-dioxygenase by 4-chloro-3-hydroxyanthranilate. Biochemistry. 2005 May 31;44(21):7623-31. PMID:15909977 doi:http://dx.doi.org/10.1021/bi0473455

[2] Wang Y, Liu KF, Yang Y, Davis I, Liu A. Observing 3-hydroxyanthranilate-3,4-dioxygenase in action through a crystalline lens. Proc Natl Acad Sci U S A. 2020 Jul 30. pii: 2005327117. doi:, 10.1073/pnas.2005327117. PMID:32732435 doi:http://dx.doi.org/10.1073/pnas.2005327117

[1]

[2]