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6q32

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The structure of the Mo-insertase domain Cnx1E (variant S269DD274S) from Arabidopsis thaliana in complex with Moco-AMP

Structural highlights

6q32 is a 1 chain structure with sequence from Arabidopsis thaliana. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.39Å
Ligands:	, , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

CNX1_ARATH Catalyzes two steps in the biosynthesis of the molybdenum cofactor. In the first step, molybdopterin is adenylated. Subsequently, molybdate is inserted into adenylated molybdopterin and AMP is released.^[1] ^[2] ^[3] ^[4]

Publication Abstract from PubMed

The molybdenum cofactor (Moco) is found in the active site of numerous important enzymes that are critical to biological processes. The bidentate ligand that chelates molybdenum in Moco is the pyranopterin dithiolene (molybdopterin, MPT). However, neither the mechanism of molybdate insertion into MPT nor the structure of Moco prior to its insertion into pyranopterin molybdenum enzymes is known. Here, we report this final maturation step, where adenylated MPT (MPT-AMP) and molybdate are the substrates. X-ray crystallography of the Arabidopsis thaliana Mo-insertase variant Cnx1E S269D D274S identified adenylated Moco (Moco-AMP) as an unexpected intermediate in this reaction sequence. X-ray absorption spectroscopy revealed the first coordination sphere geometry of Moco trapped in the Cnx1E active site. We have used this structural information to deduce a mechanism for molybdate insertion into MPT-AMP. Given their high degree of structural and sequence similarity, we suggest that this mechanism is employed by all eukaryotic Mo-insertases.

Mechanism of molybdate insertion into pterin-based molybdenum cofactors.,Probst C, Yang J, Krausze J, Hercher TW, Richers CP, Spatzal T, Kc K, Giles LJ, Rees DC, Mendel RR, Kirk ML, Kruse T Nat Chem. 2021 Aug;13(8):758-765. doi: 10.1038/s41557-021-00714-1. Epub 2021 Jun , 28. PMID:34183818^[5]

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

References

↑ Llamas A, Mendel RR, Schwarz G. Synthesis of adenylated molybdopterin: an essential step for molybdenum insertion. J Biol Chem. 2004 Dec 31;279(53):55241-6. Epub 2004 Oct 25. PMID:15504727 doi:http://dx.doi.org/10.1074/jbc.M409862200
↑ Llamas A, Otte T, Multhaup G, Mendel RR, Schwarz G. The Mechanism of nucleotide-assisted molybdenum insertion into molybdopterin. A novel route toward metal cofactor assembly. J Biol Chem. 2006 Jul 7;281(27):18343-50. Epub 2006 Apr 24. PMID:16636046 doi:http://dx.doi.org/10.1074/jbc.M601415200
↑ Kuper J, Winking J, Hecht HJ, Mendel RR, Schwarz G. The active site of the molybdenum cofactor biosynthetic protein domain Cnx1G. Arch Biochem Biophys. 2003 Mar 1;411(1):36-46. PMID:12590921
↑ Kuper J, Llamas A, Hecht HJ, Mendel RR, Schwarz G. Structure of the molybdopterin-bound Cnx1G domain links molybdenum and copper metabolism. Nature. 2004 Aug 12;430(7001):803-6. PMID:15306815 doi:10.1038/nature02681
↑ Probst C, Yang J, Krausze J, Hercher TW, Richers CP, Spatzal T, Kc K, Giles LJ, Rees DC, Mendel RR, Kirk ML, Kruse T. Mechanism of molybdate insertion into pterin-based molybdenum cofactors. Nat Chem. 2021 Aug;13(8):758-765. PMID:34183818 doi:10.1038/s41557-021-00714-1