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Protein

Vitamin D3 dihydroxylase

Gene

cyp105A1

Organism
Streptomyces griseolus
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Involved in the metabolism of vitamin D3 (calciol) and of a number of sulfonylurea herbicides. Catalyzes the two-step hydroxylation (25- and 1-alpha-hydroxylation) of vitamin D3 (VD3) to yield its active form 1-alpha,25-dihydroxyvitamin D3 (calcitriol). The first step is the hydroxylation of the C-25 position of VD3 to produce 25-hydroxyvitamin D3 (calcidiol). The second reaction is the hydroxylation of the C1-alpha-position of calcidiol to produce calcitriol. It can also hydroxylate vitamin D2.3 Publications

Catalytic activityi

Calcidiol + NADPH + O2 = calcitriol + NADP+ + H2O.3 Publications
Calciol + O2 + reduced ferredoxin = calcidiol + oxidized ferredoxin + H2O.3 Publications
Calcidiol + 2 reduced ferredoxin + 2 H+ + O2 = calcitriol + 2 oxidized ferredoxin + H2O.3 Publications

Cofactori

heme3 Publications

Kineticsi

Kcat is 0.0076 min(-1) for hydroxylase activity with 1-alpha-hydroxyvitamin D3 as substrate. Kcat is 0.0026 min(-1) for hydroxylase activity with 25-hydroxyvitamin D3 as substrate.1 Publication

Manual assertion based on experiment ini

  1. KM=0.54 µM for vitamin D3 (at pH 7.4 and 30 degrees Celsius)1 Publication
  2. KM=0.59 µM for vitamin D2 (at pH 7.4 and 30 degrees Celsius)1 Publication
  3. KM=0.91 µM for 25-hydroxyvitamin D3 (1-alpha-hydroxylation)(at pH 7.4 and 30 degrees Celsius)1 Publication
  4. KM=4.4 µM for 25-hydroxyvitamin D3 (1-alpha-hydroxylation)1 Publication
  5. KM=5 µM for 25-hydroxyvitamin D3 (1-alpha-hydroxylation)1 Publication
  6. KM=9.4 µM for 1-alpha-hydroxyvitamin D3 (25-alpha-hydroxylation)1 Publication
  7. KM=10.1 µM for 1-alpha-hydroxyvitamin D3 (25-alpha-hydroxylation)1 Publication
  1. Vmax=8.4 µmol/min/mg enzyme with 25-hydroxyvitamin D3 as substrate (1-alpha-hydroxylation)1 Publication
  2. Vmax=3.8 µmol/min/mg enzyme with as 1-alpha-hydroxyvitamin D3 substrate (25-alpha-hydroxylation)1 Publication
  3. Vmax=3.6 mmol/min/mg enzyme with 25-hydroxyvitamin D3 as substrate (1-alpha-hydroxylation)(at pH 7.4 and 30 degrees Celsius)1 Publication
  4. Vmax=16 mmol/min/mg enzyme with vitamin D3 as substrate (at pH 7.4 and 30 degrees Celsius)1 Publication
  5. Vmax=84 mmol/min/mg enzyme with vitamin D2 as substrate (at pH 7.4 and 30 degrees Celsius)1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei81Vitamin D31 Publication1
Binding sitei103Heme1 Publication1
Binding sitei107Heme1 Publication1
Binding sitei193Vitamin D32 Publications1
Binding sitei236Vitamin D31 Publication1
Binding sitei293Vitamin D3; via carbonyl oxygen2 Publications1
Binding sitei297Heme1 Publication1
Binding sitei353Heme1 Publication1
Metal bindingi355Iron (heme axial ligand)1 Publication1

GO - Molecular functioni

GO - Biological processi

  • vitamin D3 metabolic process Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Monooxygenase, Oxidoreductase

Keywords - Ligandi

Heme, Iron, Metal-binding, NADP

Names & Taxonomyi

Protein namesi
Recommended name:
Vitamin D3 dihydroxylaseCurated (EC:1.14.15.-3 Publications)
Alternative name(s):
CYP105A11 Publication
Cytochrome P450-CVA11 Publication
Cytochrome P450-SU11 Publication
Vitamin D3 hydroxylase1 Publication
Short name:
VD3 hydroxylase1 Publication
Gene namesi
Name:cyp105A11 Publication
Synonyms:suaC1 Publication
OrganismiStreptomyces griseolus
Taxonomic identifieri1909 [NCBI]
Taxonomic lineageiBacteriaActinobacteriaStreptomycetalesStreptomycetaceaeStreptomyces

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi73R → A, F, L or V: Increase of the hydroxylase activity and decrease of affinity for both 25-hydroxyvitamin D3 and 1-alpha-hydroxyvitamin D3. Increase of the hydroxylase activity; when associated with A-84 and F-84. 2 Publications1
Mutagenesisi84R → A, Q, L or F: Increase of the hydroxylase activity and decrease of affinity for both 25-hydroxyvitamin D3 and 1-alpha-hydroxyvitamin D3. Increase of the hydroxylase activity; when associated with A-73 and V-73. 1 Publication1
Mutagenesisi84R → F: Alters the substrate specificity that gives preference to the 1-alpha-hydroxylation of 25-hydroxyvitamin D3 over the 25-hydroxylation of 1-alpha-hydroxyvitamin D3. Increase of the hydroxylase activity and decrease of affinity for both 25-hydroxyvitamin D3 and 1-alpha-hydroxyvitamin D3. 1 Publication1
Mutagenesisi88V → A: Decrease of the hydroxylase activity for both 25-hydroxyivitamin D3 and 1-alpha-hydroxyvitamin D3. 1 Publication1
Mutagenesisi180L → A: Decrease of the hydroxylase activity for both 25-hydroxyvitamin D3 and 1-alpha-hydroxyvitamin D3. 1 Publication1
Mutagenesisi181V → A: Decrease of the hydroxylase activity for both 25-hydroxyvitamin D3 and 1-alpha-hydroxyvitamin D3. 1 Publication1
Mutagenesisi193R → A, Q or K: Decrease of the hydroxylase activity. 1 Publication1
Mutagenesisi293I → A: Slight increase of the hydroxylase activity. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemoved2 Publications
ChainiPRO_00000522132 – 406Vitamin D3 dihydroxylaseAdd BLAST405

Expressioni

Inductioni

By herbicides.1 Publication

Structurei

Secondary structure

1406
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi15 – 17Combined sources3
Helixi28 – 35Combined sources8
Beta strandi36 – 44Combined sources9
Beta strandi50 – 54Combined sources5
Helixi57 – 64Combined sources8
Helixi83 – 85Combined sources3
Turni88 – 90Combined sources3
Helixi95 – 97Combined sources3
Helixi102 – 107Combined sources6
Turni108 – 110Combined sources3
Helixi111 – 114Combined sources4
Helixi116 – 140Combined sources25
Beta strandi142 – 145Combined sources4
Helixi146 – 149Combined sources4
Turni150 – 152Combined sources3
Helixi153 – 163Combined sources11
Helixi167 – 169Combined sources3
Helixi170 – 182Combined sources13
Helixi186 – 209Combined sources24
Helixi215 – 221Combined sources7
Turni222 – 227Combined sources6
Helixi231 – 261Combined sources31
Helixi264 – 272Combined sources9
Helixi274 – 276Combined sources3
Helixi277 – 288Combined sources12
Helixi292 – 294Combined sources3
Beta strandi296 – 301Combined sources6
Beta strandi303 – 305Combined sources3
Beta strandi308 – 310Combined sources3
Beta strandi315 – 318Combined sources4
Helixi320 – 323Combined sources4
Turni327 – 329Combined sources3
Beta strandi330 – 332Combined sources3
Helixi358 – 375Combined sources18
Beta strandi380 – 383Combined sources4
Helixi385 – 387Combined sources3
Beta strandi398 – 400Combined sources3
Beta strandi403 – 405Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2ZBXX-ray1.50A1-406[»]
2ZBYX-ray1.60A1-406[»]
2ZBZX-ray1.90A1-406[»]
3CV8X-ray2.00A1-406[»]
3CV9X-ray1.70A1-406[»]
ProteinModelPortaliP18326.
SMRiP18326.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP18326.

Family & Domainsi

Sequence similaritiesi

Belongs to the cytochrome P450 family.Curated

Family and domain databases

Gene3Di1.10.630.10. 1 hit.
InterProiIPR001128. Cyt_P450.
IPR002397. Cyt_P450_B.
IPR017972. Cyt_P450_CS.
[Graphical view]
PfamiPF00067. p450. 1 hit.
[Graphical view]
PRINTSiPR00359. BP450.
PR00385. P450.
SUPFAMiSSF48264. SSF48264. 1 hit.
PROSITEiPS00086. CYTOCHROME_P450. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P18326-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MTDTATTPQT TDAPAFPSNR SCPYQLPDGY AQLRDTPGPL HRVTLYDGRQ
60 70 80 90 100
AWVVTKHEAA RKLLGDPRLS SNRTDDNFPA TSPRFEAVRE SPQAFIGLDP
110 120 130 140 150
PEHGTRRRMT ISEFTVKRIK GMRPEVEEVV HGFLDEMLAA GPTADLVSQF
160 170 180 190 200
ALPVPSMVIC RLLGVPYADH EFFQDASKRL VQSTDAQSAL TARNDLAGYL
210 220 230 240 250
DGLITQFQTE PGAGLVGALV ADQLANGEID REELISTAML LLIAGHETTA
260 270 280 290 300
SMTSLSVITL LDHPEQYAAL RADRSLVPGA VEELLRYLAI ADIAGGRVAT
310 320 330 340 350
ADIEVEGHLI RAGEGVIVVN SIANRDGTVY EDPDALDIHR SARHHLAFGF
360 370 380 390 400
GVHQCLGQNL ARLELEVILN ALMDRVPTLR LAVPVEQLVL RPGTTIQGVN

ELPVTW
Length:406
Mass (Da):44,212
Last modified:January 23, 2007 - v2
Checksum:iB41CDD7B9BC56191
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M32238 Genomic DNA. Translation: AAA26823.1.
PIRiA35401.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M32238 Genomic DNA. Translation: AAA26823.1.
PIRiA35401.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2ZBXX-ray1.50A1-406[»]
2ZBYX-ray1.60A1-406[»]
2ZBZX-ray1.90A1-406[»]
3CV8X-ray2.00A1-406[»]
3CV9X-ray1.70A1-406[»]
ProteinModelPortaliP18326.
SMRiP18326.
ModBaseiSearch...
MobiDBiSearch...

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Miscellaneous databases

EvolutionaryTraceiP18326.

Family and domain databases

Gene3Di1.10.630.10. 1 hit.
InterProiIPR001128. Cyt_P450.
IPR002397. Cyt_P450_B.
IPR017972. Cyt_P450_CS.
[Graphical view]
PfamiPF00067. p450. 1 hit.
[Graphical view]
PRINTSiPR00359. BP450.
PR00385. P450.
SUPFAMiSSF48264. SSF48264. 1 hit.
PROSITEiPS00086. CYTOCHROME_P450. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiCPXE_STRGO
AccessioniPrimary (citable) accession number: P18326
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1990
Last sequence update: January 23, 2007
Last modified: November 30, 2016
This is version 90 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programProkaryotic Protein Annotation Program

Miscellaneousi

Miscellaneous

Two metabolic pathways exist. One is a conversion of VD3 to 25-hydroxyvitamin D3 and then to 1-alpha,25-dihydroxyvitamin D3 (25-pathway), while the other one is a pathway via 1-alpha-hydroxyvitamin D3 as an intermediate (1-alpha-pathway). Analysis show that the amount of 25-hydroxyvitamin D3 is predominant as the product of this reaction, while very small amounts of 1-alpha-hydroxyvitamin D3 and 1-alpha,25-dihydroxyvitamin D3 are obtained, suggesting that the major pathway is the 25-pathway.1 Publication
The hydrophobicity and the volume of the side chain at position 84 are critical for the activity.1 Publication

Keywords - Technical termi

3D-structure, Direct protein sequencing

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.