| Structural highlights
4s26 is a 2 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 1.85Å |
| Ligands: | , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
THIC_ARATH Catalyzes the synthesis of the hydroxymethylpyrimidine phosphate (HMP-P) moiety of thiamine from aminoimidazole ribotide (AIR) in a radical S-adenosyl-L-methionine (SAM)-dependent reaction.[1] [2]
Publication Abstract from PubMed
Radical S-adenosylmethionine (SAM) enzymes use a [4Fe-4S] cluster to generate a 5'-deoxyadenosyl radical. Canonical radical SAM enzymes are characterized by a beta-barrel-like fold and SAM anchors to the differentiated iron of the cluster, which is located near the amino terminus and within the beta-barrel, through its amino and carboxylate groups. Here we show that ThiC, the thiamin pyrimidine synthase in plants and bacteria, contains a tethered cluster-binding domain at its carboxy terminus that moves in and out of the active site during catalysis. In contrast to canonical radical SAM enzymes, we predict that SAM anchors to an additional active site metal through its amino and carboxylate groups. Superimposition of the catalytic domains of ThiC and glutamate mutase shows that these two enzymes share similar active site architectures, thus providing strong evidence for an evolutionary link between the radical SAM and adenosylcobalamin-dependent enzyme superfamilies.
Non-canonical active site architecture of the radical SAM thiamin pyrimidine synthase.,Fenwick MK, Mehta AP, Zhang Y, Abdelwahed SH, Begley TP, Ealick SE Nat Commun. 2015 Mar 27;6:6480. doi: 10.1038/ncomms7480. PMID:25813242[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Raschke M, Burkle L, Muller N, Nunes-Nesi A, Fernie AR, Arigoni D, Amrhein N, Fitzpatrick TB. Vitamin B1 biosynthesis in plants requires the essential iron sulfur cluster protein, THIC. Proc Natl Acad Sci U S A. 2007 Dec 4;104(49):19637-42. Epub 2007 Nov 28. PMID:18048325 doi:http://dx.doi.org/10.1073/pnas.0709597104
- ↑ Kong D, Zhu Y, Wu H, Cheng X, Liang H, Ling HQ. AtTHIC, a gene involved in thiamine biosynthesis in Arabidopsis thaliana. Cell Res. 2008 May;18(5):566-76. doi: 10.1038/cr.2008.35. PMID:18332905 doi:http://dx.doi.org/10.1038/cr.2008.35
- ↑ Fenwick MK, Mehta AP, Zhang Y, Abdelwahed SH, Begley TP, Ealick SE. Non-canonical active site architecture of the radical SAM thiamin pyrimidine synthase. Nat Commun. 2015 Mar 27;6:6480. doi: 10.1038/ncomms7480. PMID:25813242 doi:http://dx.doi.org/10.1038/ncomms7480
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