Reviewed, UniProtKB/Swiss-Prot P0A512 (CP51_MYCTU)

Names and origin

Protein names

Recommended name:
    Lanosterol 14-alpha demethylase
    EC=1.14.13.70
Alternative name(s):
    Cytochrome P450 51
    CYPLI
    P450-LIA1
    Sterol 14-alpha demethylase
    P450-14DM

Gene names

Name:	cyp51
Ordered Locus Names:	Rv0764c, MT0788
ORF Names:	MTCY369.09c

Organism

Mycobacterium tuberculosis [Complete proteome] [HAMAP]

Taxonomic identifier

1773 [NCBI]

Taxonomic lineage

Bacteria › Actinobacteria › Actinobacteridae › Actinomycetales › Corynebacterineae › Mycobacteriaceae › Mycobacterium › Mycobacterium tuberculosis complex

Protein attributes

Sequence length	451 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Its precise biological substrate is not known. Catalyzes C14-demethylation of lanosterol, 24,25-dihydrolanosterol and obtusifoliol which is critical for ergosterol biosynthesis. It transforms lanosterol into 4,4'-dimethyl cholesta-8,14,24-triene-3-beta-ol.
Catalytic activity	Obtusifoliol + 3 O2 + 3 NADPH = 4-alpha-methyl-5-alpha-ergosta-8,14,24(28)-trien-3-beta-ol + formate + 3 NADP+ + 4 H2O.
Cofactor	Heme group.
Pathway	Steroid biosynthesis; zymosterol biosynthesis; zymosterol from lanosterol: step 1/6.
Subunit structure	Monomer Probable.
Subcellular location	Cytoplasm.
Sequence similarities	Belongs to the cytochrome P450 family.

Ontologies

Keywords
Biological process	Lipid synthesis Steroid biosynthesis Sterol biosynthesis
Cellular component	Cytoplasm
Ligand	Heme Iron Metal-binding NADP
Molecular function	Monooxygenase Oxidoreductase
Technical term	3D-structure Complete proteome
Gene Ontology (GO)
Biological process	oxidation reduction Inferred from electronic annotation. Source: UniProtKB-KW sterol biosynthetic process Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	electron carrier activity Inferred from electronic annotation. Source: InterPro heme binding Inferred from electronic annotation. Source: InterPro sterol 14-demethylase activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 451

451

Lanosterol 14-alpha demethylase

PRO_0000052017

Sites

Metal binding

394

1

Iron (heme axial ligand)

Secondary structure

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451

Helix Strand Turn

Details...

Helix

19 – 24

6

Helix

26 – 37

12

Beta strand

39 – 45

7

Beta strand

48 – 53

6

Helix

55 – 64

10

Turn

67 – 69

3

Helix

77 – 79

3

Helix

80 – 83

4

Helix

93 – 101

9

Turn

102 – 105

4

Helix

107 – 125

19

Beta strand

130 – 135

6

Helix

136 – 152

17

Helix

155 – 158

4

Helix

163 – 174

12

Helix

178 – 181

4

Helix

189 – 214

26

Beta strand

218 – 220

3

Helix

225 – 231

7

Beta strand

237 – 240

4

Helix

243 – 274

32

Helix

276 – 289

14

Helix

290 – 292

3

Helix

296 – 299

4

Helix

305 – 317

13

Beta strand

324 – 330

7

Beta strand

332 – 334

3

Beta strand

337 – 339

3

Beta strand

344 – 347

4

Helix

349 – 352

4

Turn

356 – 358

3

Beta strand

359 – 361

3

Helix

367 – 370

4

Turn

372 – 374

3

Helix

376 – 379

4

Turn

381 – 383

3

Helix

390 – 392

3

Helix

397 – 414

18

Beta strand

415 – 421

7

Helix

423 – 425

3

Beta strand

431 – 434

4

Beta strand

442 – 447

6

Sequences

	Sequence		Length	Mass (Da)
	P0A512-1 [UniParc]. Last modified March 15, 2005. Version 1. Checksum: B3D671EA9542A57B	FASTA	451	50,878
	10 20 30 40 50 60 MSAVALPRVS GGHDEHGHLE EFRTDPIGLM QRVRDECGDV GTFQLAGKQV VLLSGSHANE 70 80 90 100 110 120 FFFRAGDDDL DQAKAYPFMT PIFGEGVVFD ASPERRKEML HNAALRGEQM KGHAATIEDQ 130 140 150 160 170 180 VRRMIADWGE AGEIDLLDFF AELTIYTSSA CLIGKKFRDQ LDGRFAKLYH ELERGTDPLA 190 200 210 220 230 240 YVDPYLPIES FRRRDEARNG LVALVADIMN GRIANPPTDK SDRDMLDVLI AVKAETGTPR 250 260 270 280 290 300 FSADEITGMF ISMMFAGHHT SSGTASWTLI ELMRHRDAYA AVIDELDELY GDGRSVSFHA 310 320 330 340 350 360 LRQIPQLENV LKETLRLHPP LIILMRVAKG EFEVQGHRIH EGDLVAASPA ISNRIPEDFP 370 380 390 400 410 420 DPHDFVPARY EQPRQEDLLN RWTWIPFGAG RHRCVGAAFA IMQIKAIFSV LLREYEFEMA 430 440 450 QPPESYRNDH SKMVVQLAQP ACVRYRRRTG V

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence." Cole S.T., Brosch R., Parkhill J., Garnier T., Churcher C.M., Harris D.E., Gordon S.V., Eiglmeier K., Gas S., Barry C.E. III, Tekaia F., Badcock K., Basham D., Brown D., Chillingworth T., Connor R., Davies R.M., Devlin K. , Feltwell T., Gentles S., Hamlin N., Holroyd S., Hornsby T., Jagels K., Krogh A., McLean J., Moule S., Murphy L.D., Oliver S., Osborne J., Quail M.A., Rajandream M.A., Rogers J., Rutter S., Seeger K., Skelton S., Squares S., Squares R., Sulston J.E., Taylor K., Whitehead S., Barrell B.G. Nature 393:537-544(1998) [PubMed: 9634230] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: ATCC 25618 / H37Rv.
[2]	"Whole-genome comparison of Mycobacterium tuberculosis clinical and laboratory strains." Fleischmann R.D., Alland D., Eisen J.A., Carpenter L., White O., Peterson J.D., DeBoy R.T., Dodson R.J., Gwinn M.L., Haft D.H., Hickey E.K., Kolonay J.F., Nelson W.C., Umayam L.A., Ermolaeva M.D., Salzberg S.L., Delcher A., Utterback T.R. , Weidman J.F., Khouri H.M., Gill J., Mikula A., Bishai W., Jacobs W.R. Jr., Venter J.C., Fraser C.M. J. Bacteriol. 184:5479-5490(2002) [PubMed: 12218036] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: CDC 1551 / Oshkosh.
[3]	"CYP51-like gene of Mycobacterium tuberculosis actually encodes a P450 similar to eukaryotic CYP51." Aoyama Y., Horiuchi T., Gotoh O., Noshiro M., Yoshida Y. J. Biochem. 124:694-696(1998) [PubMed: 9756611] [Abstract] Cited for: CHARACTERIZATION.
[4]	"Characterization and catalytic properties of the sterol 14 alpha-demethylase from Mycobacterium tuberculosis." Bellamine A., Mangla A.T., Nes W.D., Waterman M.R. Proc. Natl. Acad. Sci. U.S.A. 96:8937-8942(1999) [PubMed: 10430874] [Abstract] Cited for: CHARACTERIZATION.
[5]	"Structural requirements for substrate recognition of Mycobacterium tuberculosis 14alpha-demethylase: implications for sterol biosynthesis." Bellamine A., Mangla A.T., Dennis A.L., Nes W.D., Waterman M.R. J. Lipid Res. 42:128-136(2001) [PubMed: 11160374] [Abstract] Cited for: CHARACTERIZATION.
[6]	"Crystal structure of cytochrome P450 14 alpha-sterol demethylase (CYP51) from Mycobacterium tuberculosis in complex with azole inhibitors." Podust L.M., Poulos T.L., Waterman M.R. Proc. Natl. Acad. Sci. U.S.A. 98:3068-3073(2001) [PubMed: 11248033] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS).
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

BX842574 Genomic DNA. Translation: CAB02394.1.
AE000516 Genomic DNA. Translation: AAK45030.1.

PIR

G70706.

RefSeq

NP_215278.1.
NP_335216.1.

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1E9X	X-ray	2.10	A	1-451	[»]
1EA1	X-ray	2.21	A	1-451	[»]
1H5Z	X-ray	2.05	A	1-451	[»]
1U13	X-ray	2.01	A	1-451	[»]
1X8V	X-ray	1.55	A	1-451	[»]
2BZ9	X-ray	2.21	A/B	1-451	[»]
2CI0	X-ray	1.53	A	1-451	[»]
2CIB	X-ray	1.50	A	1-451	[»]
2VKU	X-ray	1.95	A	1-451	[»]
2W09	X-ray	1.57	A	1-451	[»]
2W0A	X-ray	1.60	A	1-451	[»]
2W0B	X-ray	1.56	A	1-451	[»]

ModBase

Search...

Genome annotation databases

GeneID

888819.
926091.

GenomeReviews

Gene locus MT0788 in contig AE000516_GR.
Gene locus Rv0764c in contig AL123456_GR.

KEGG

mtc:MT0788.
mtu:Rv0764c.

TIGR

MT0788.

Organism-specific databases

TubercuList

Rv0764c.

Phylogenomic databases

HOGENOM

P0A512.

OMA

P0A512. MEQVTGG.

Enzyme and pathway databases

BRENDA

1.14.13.70. 809.

Family and domain databases

InterPro

IPR001128. Cyt_P450.
IPR017973. Cyt_P450_C.
IPR017972. Cyt_P450_CS.
IPR002403. Cyt_P450_E_grp-IV.
[Graphical view]

Gene3D

G3DSA:1.10.630.10. Cyt_P450. 1 hit.

PANTHER

PTHR19383. Cyt_P450. 1 hit.

Pfam

PF00067. p450. 1 hit.
[Graphical view]

PRINTS

PR00465. EP450IV.
PR00385. P450.

PROSITE

PS00086. CYTOCHROME_P450. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

DrugBank

DB04573. Estriol.

Entry information

Entry name

CP51_MYCTU

Accession

Primary (citable) accession number: P0A512
Secondary accession number(s): P77901

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 15, 2005
Last sequence update:	March 15, 2005
Last modified:	June 16, 2009
This is version 43 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HAMAP (High-quality Automated and Manual Annotation of microbial Proteomes)