Structural highlights
4s2a is a 1 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
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| Ligands: | , |
| Related: | 4n7q, 3epm, 3epn, 3epo, 4s25, 4s26, 4s27, 4s28, 4s29 |
| Activity: | Phosphomethylpyrimidine synthase, with EC number 4.1.99.17 |
| Resources: | FirstGlance, OCA, RCSB, PDBsum |
Function
[THIC_CAUCR] 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]
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[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Chatterjee A, Li Y, Zhang Y, Grove TL, Lee M, Krebs C, Booker SJ, Begley TP, Ealick SE. Reconstitution of ThiC in thiamine pyrimidine biosynthesis expands the radical SAM superfamily. Nat Chem Biol. 2008 Dec;4(12):758-65. Epub 2008 Oct 26. PMID:18953358 doi:10.1038/nchembio.121
- ↑ 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
