Enzymes
UniProtKB help_outline | 7 proteins |
Reaction participants Show >> << Hide
- Name help_outline 19-oxo-androst-4-ene-3,17-dione Identifier CHEBI:799 (CAS: 968-49-0) help_outline Charge 0 Formula C19H24O3 InChIKeyhelp_outline XRCFMDPVHKVRDJ-BGJMDTOESA-N SMILEShelp_outline [H][C@@]12CCC3=CC(=O)CC[C@]3(C=O)[C@@]1([H])CC[C@]1(C)C(=O)CC[C@@]21[H] 2D coordinates Mol file for the small molecule Search links Involved in 2 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline O2 Identifier CHEBI:15379 (CAS: 7782-44-7) help_outline Charge 0 Formula O2 InChIKeyhelp_outline MYMOFIZGZYHOMD-UHFFFAOYSA-N SMILEShelp_outline O=O 2D coordinates Mol file for the small molecule Search links Involved in 2,648 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
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Namehelp_outline
reduced [NADPH—hemoprotein reductase]
Identifier
RHEA-COMP:11964
Reactive part
help_outline
- Name help_outline FMNH2 Identifier CHEBI:57618 (Beilstein: 6258176) help_outline Charge -2 Formula C17H21N4O9P InChIKeyhelp_outline YTNIXZGTHTVJBW-SCRDCRAPSA-L SMILEShelp_outline Cc1cc2Nc3c([nH]c(=O)[nH]c3=O)N(C[C@H](O)[C@H](O)[C@H](O)COP([O-])([O-])=O)c2cc1C 2D coordinates Mol file for the small molecule Search links Involved in 771 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline estrone Identifier CHEBI:17263 (Beilstein: 1915077; CAS: 53-16-7) help_outline Charge 0 Formula C18H22O2 InChIKeyhelp_outline DNXHEGUUPJUMQT-CBZIJGRNSA-N SMILEShelp_outline [H][C@]12CC[C@]3(C)C(=O)CC[C@@]3([H])[C@]1([H])CCc1cc(O)ccc21 2D coordinates Mol file for the small molecule Search links Involved in 16 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline formate Identifier CHEBI:15740 (Beilstein: 1901205; CAS: 71-47-6) help_outline Charge -1 Formula CHO2 InChIKeyhelp_outline BDAGIHXWWSANSR-UHFFFAOYSA-M SMILEShelp_outline [H]C([O-])=O 2D coordinates Mol file for the small molecule Search links Involved in 96 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline H+ Identifier CHEBI:15378 Charge 1 Formula H InChIKeyhelp_outline GPRLSGONYQIRFK-UHFFFAOYSA-N SMILEShelp_outline [H+] 2D coordinates Mol file for the small molecule Search links Involved in 9,176 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline H2O Identifier CHEBI:15377 (Beilstein: 3587155; CAS: 7732-18-5) help_outline Charge 0 Formula H2O InChIKeyhelp_outline XLYOFNOQVPJJNP-UHFFFAOYSA-N SMILEShelp_outline [H]O[H] 2D coordinates Mol file for the small molecule Search links Involved in 6,048 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
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Namehelp_outline
oxidized [NADPH—hemoprotein reductase]
Identifier
RHEA-COMP:11965
Reactive part
help_outline
- Name help_outline FMN Identifier CHEBI:58210 Charge -3 Formula C17H18N4O9P InChIKeyhelp_outline ANKZYBDXHMZBDK-SCRDCRAPSA-K SMILEShelp_outline C12=NC([N-]C(C1=NC=3C(N2C[C@@H]([C@@H]([C@@H](COP(=O)([O-])[O-])O)O)O)=CC(=C(C3)C)C)=O)=O 2D coordinates Mol file for the small molecule Search links Involved in 781 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
Cross-references
RHEA:38207 | RHEA:38208 | RHEA:38209 | RHEA:38210 | |
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Reaction direction help_outline | undefined | left-to-right | right-to-left | bidirectional |
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MetaCyc help_outline |
Publications
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Mechanism of estrogen biosynthesis. Participation of multiple enzyme sites in placental aromatase hydroxylations.
Fishman J., Goto J.
J Biol Chem 256:4466-4471(1981) [PubMed] [EuropePMC]
This publication is cited by 7 other entries.
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Kinetic analysis of the three-step steroid aromatase reaction of human cytochrome P450 19A1.
Sohl C.D., Guengerich F.P.
Cytochrome P450 19A1 (P450 19A1), the aromatase, catalyzes the conversion of androgens to estrogens through a sequential three-step reaction, generating 19-hydroxy and 19-aldehyde intermediates en route to the product estrogen. A procedure for the heterologous expression and purification of P450 1 ... >> More
Cytochrome P450 19A1 (P450 19A1), the aromatase, catalyzes the conversion of androgens to estrogens through a sequential three-step reaction, generating 19-hydroxy and 19-aldehyde intermediates en route to the product estrogen. A procedure for the heterologous expression and purification of P450 19A1 in Escherichia coli was developed (k(cat) of 0.06 s(-1) for the conversion of androstenedione to estrone). Binding of the substrate and intermediates show low micromolar dissociation constants and are at least two-step processes. Rates of reduction of the iron were fast in the presence of substrate, either intermediate, or product. P450 19A1 is a distributive rather than a processive enzyme, with the sequential reaction allowing free dissociation of the intermediates as revealed by pulse-chase experiments. Conversion of androstenedione to estrone (under single turnover conditions) generated a progress curve showing changes in the concentrations of the substrate, intermediates, and product. A minimal kinetic model containing the individual rate constants for the steps in P450 19A1 catalysis was developed to globally fit the time course of the overall reaction, the dissociation constants, the two-step ligand binding, the distributive character, the iron-reduction rates, and the steady-state conversion of the 19-hydroxy androstenedione and 19-aldehyde androstenedione intermediates to estrone. << Less
J. Biol. Chem. 285:17734-17743(2010) [PubMed] [EuropePMC]
This publication is cited by 2 other entries.
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Structural basis for androgen specificity and oestrogen synthesis in human aromatase.
Ghosh D., Griswold J., Erman M., Pangborn W.
Aromatase cytochrome P450 is the only enzyme in vertebrates known to catalyse the biosynthesis of all oestrogens from androgens. Aromatase inhibitors therefore constitute a frontline therapy for oestrogen-dependent breast cancer. In a three-step process, each step requiring 1 mol of O(2), 1 mol of ... >> More
Aromatase cytochrome P450 is the only enzyme in vertebrates known to catalyse the biosynthesis of all oestrogens from androgens. Aromatase inhibitors therefore constitute a frontline therapy for oestrogen-dependent breast cancer. In a three-step process, each step requiring 1 mol of O(2), 1 mol of NADPH, and coupling with its redox partner cytochrome P450 reductase, aromatase converts androstenedione, testosterone and 16alpha-hydroxytestosterone to oestrone, 17beta-oestradiol and 17beta,16alpha-oestriol, respectively. The first two steps are C19-methyl hydroxylation steps, and the third involves the aromatization of the steroid A-ring, unique to aromatase. Whereas most P450s are not highly substrate selective, it is the hallmark androgenic specificity that sets aromatase apart. The structure of this enzyme of the endoplasmic reticulum membrane has remained unknown for decades, hindering elucidation of the biochemical mechanism. Here we present the crystal structure of human placental aromatase, the only natural mammalian, full-length P450 and P450 in hormone biosynthetic pathways to be crystallized so far. Unlike the active sites of many microsomal P450s that metabolize drugs and xenobiotics, aromatase has an androgen-specific cleft that binds the androstenedione molecule snugly. Hydrophobic and polar residues exquisitely complement the steroid backbone. The locations of catalytically important residues shed light on the reaction mechanism. The relative juxtaposition of the hydrophobic amino-terminal region and the opening to the catalytic cleft shows why membrane anchoring is necessary for the lipophilic substrates to gain access to the active site. The molecular basis for the enzyme's androgenic specificity and unique catalytic mechanism can be used for developing next-generation aromatase inhibitors. << Less
Nature 457:219-223(2009) [PubMed] [EuropePMC]
This publication is cited by 7 other entries.
Comments
RHEA:38207 part of RHEA:38195