7rom

Structural highlights

Function

NCB5R_YEAST NADH-dependent reductase for KTI11/DPH3 and cytochrome b5 (PubMed:14930, PubMed:10622712, PubMed:27694803, PubMed:31463593, PubMed:34154323). Required for the first step of diphthamide biosynthesis, a post-translational modification of histidine which occurs in elongation factor 2 (PubMed:31463593, PubMed:34154323, PubMed:27694803). DPH1 and DPH2 transfer a 3-amino-3-carboxypropyl (ACP) group from S-adenosyl-L-methionine (SAM) to a histidine residue, the reaction is assisted by a reduction system comprising KTI11/DPH3 and a NADH-dependent reductase, predominantly CBR1 (PubMed:31463593, PubMed:34154323). By reducing KTI11/DPH3, also involved in the formation of the tRNA wobble base modification mcm5s 2U (5-methoxycarbonylmethyl-2-thiouridine), mediated by the elongator complex (PubMed:27694803). The cytochrome b5/NADH cytochrome b5 reductase electron transfer system supports the catalytic activity of several sterol biosynthetic enzymes (PubMed:10622712). Plays a role in bud morphology (PubMed:17895367).^{[1] [2] [3] [4] [5] [6]}

See Also

• NADH-cytochrome b5 reductase

References

1. ↑ Lamb DC, Kelly DE, Manning NJ, Kaderbhai MA, Kelly SL. Biodiversity of the P450 catalytic cycle: yeast cytochrome b5/NADH cytochrome b5 reductase complex efficiently drives the entire sterol 14-demethylation (CYP51) reaction. FEBS Lett. 1999 Dec 3;462(3):283-8. PMID:10622712 doi:10.1016/s0014-5793(99)01548-3
2. ↑ Kubota S, Yoshida Y, Kumaoka H. Studies on the microsomal electron-transport system of anaerobically grown yeast. IV. Purification and characterization of NADH-cytochrome b5 reductase. J Biochem. 1977 Jan;81(1):187-95. PMID:14930 doi:10.1093/oxfordjournals.jbchem.a131434
3. ↑ Tiedje C, Holland DG, Just U, Höfken T. Proteins involved in sterol synthesis interact with Ste20 and regulate cell polarity. J Cell Sci. 2007 Oct 15;120(Pt 20):3613-24. PMID:17895367 doi:10.1242/jcs.009860
4. ↑ Lin Z, Dong M, Zhang Y, Lee EA, Lin H. Cbr1 is a Dph3 reductase required for the tRNA wobble uridine modification. Nat Chem Biol. 2016 Dec;12(12):995-997. PMID:27694803 doi:10.1038/nchembio.2190
5. ↑ Dong M, Dando EE, Kotliar I, Su X, Dzikovski B, Freed JH, Lin H. The asymmetric function of Dph1-Dph2 heterodimer in diphthamide biosynthesis. J Biol Inorg Chem. 2019 Sep;24(6):777-782. PMID:31463593 doi:10.1007/s00775-019-01702-0
6. ↑ Zhang Y, Su D, Dzikovski B, Majer SH, Coleman R, Chandrasekaran S, Fenwick MK, Crane BR, Lancaster KM, Freed JH, Lin H. Dph3 Enables Aerobic Diphthamide Biosynthesis by Donating One Iron Atom to Transform a [3Fe-4S] to a [4Fe-4S] Cluster in Dph1-Dph2. J Am Chem Soc. 2021 Jun 30;143(25):9314-9319. PMID:34154323 doi:10.1021/jacs.1c03956