Details of Drug-Metabolizing Enzyme (DME)

General Information of DME (ID: DMEN027)
DME Name Vitamin D3 dihydroxylase (cyp105A1), Streptomyces griseolus
Gene Name cyp105A1
UniProt ID
CPXE_STRGO
Lineage    Species: Streptomyces griseolus     (Click to Show/Hide the Complete Species Lineage)
Kingdom: Bacteria
Phylum: Actinomycetota
Class: Actinomycetes
Order: Streptomycetales
Family: Streptomycetaceae
Genus: Streptomyces
Species: Streptomyces griseolus
      Click to Show/Hide the Molecular/Functional Data (Sequence/Structure/Pathway/Function) of This DME
Sequence
MTDTATTPQTTDAPAFPSNRSCPYQLPDGYAQLRDTPGPLHRVTLYDGRQAWVVTKHEAA
RKLLGDPRLSSNRTDDNFPATSPRFEAVRESPQAFIGLDPPEHGTRRRMTISEFTVKRIK
GMRPEVEEVVHGFLDEMLAAGPTADLVSQFALPVPSMVICRLLGVPYADHEFFQDASKRL
VQSTDAQSALTARNDLAGYLDGLITQFQTEPGAGLVGALVADQLANGEIDREELISTAML
LLIAGHETTASMTSLSVITLLDHPEQYAALRADRSLVPGAVEELLRYLAIADIAGGRVAT
ADIEVEGHLIRAGEGVIVVNSIANRDGTVYEDPDALDIHRSARHHLAFGFGVHQCLGQNL
ARLELEVILNALMDRVPTLRLAVPVEQLVLRPGTTIQGVNELPVTW
Structure
2ZBX ; 2ZBY ; 2ZBZ ; 3CV8 ; 3CV9 ; 5X7E ;
Function 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.
Full List of Drug(s) Metabolized by This DME
      Drugs Approved by FDA Click to Show/Hide the Full List of Drugs:          3 Drugs
Meclofenamate sodium
 Drug Info Approved Rheumatoid arthritis ICD11: FA20 [1]
Meclofenamic acid
 Drug Info Approved Myalgia ICD11: FB56 [1]
Flufenamic Acid
 Drug Info Approved Female pelvic pain ICD11: GA34 [1]
      Drugs in Phase 1 Clinical Trial Click to Show/Hide the Full List of Drugs:          1 Drugs
GEA-6414
 Drug Info Phase 1/2 Parkinsonism ICD11: 8A00 [1]
Full List of Metabolic Reactions (MR) Catalyzed by This DME
MR ID Reactant Product MR Type Source Drug REF
MR006114 GEA-6414 Tolfenamic acid M1 Oxidation - 4-hydroxylation GEA-6414 [1]
MR013708 Meclofenamate sodium Meclofenamate sodium metabolite M1 Oxidation - 4-hydroxylation Meclofenamate sodium [1]
MR001613 Meclofenamic acid 3-hydroxymethyl Mefenamic Acid Oxidation - Hydroxylation Meclofenamic acid [1]
References
1 Metabolism of non-steroidal anti-inflammatory drugs (NSAIDs) by Streptomyces griseolus CYP105A1 and its variants Drug Metab Pharmacokinet. 2022 Aug;45:100455. doi: 10.1016/j.dmpk.2022.100455.

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