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1.14.14.16: steroid 21-monooxygenase

This is an abbreviated version!
For detailed information about steroid 21-monooxygenase, go to the full flat file.

Word Map on EC 1.14.14.16

Reaction

a C21 steroid
+
[reduced NADPH-hemoprotein reductase]
 +
O2
=
a 21-hydroxy-C21-steroid
 +
[oxidized NADPH-hemoprotein reductase]
 +
H2O

Synonyms

17alpha-hydroxyprogesterone 21-hydrolase, 21-hydroxylase, 21-hydroxylase cytochrome P-450, 21OH, C3B21RA protein, CYP21, CYP21A2, CYP2D, Cytochrome P-450 specific for steroid C-21 hydroxylation, cytochrome P-450-linked mixed function oxidase system, cytochrome P-450C-21, cytochrome p450 21A2, cytochrome P450 steroid 21-hydroxylase, cytochrome P450c21, EC 1.14.1.8, EC 1.14.99.10, EC 1.99.1.11, P-450(C21), P450 oxidoreductase-21-hydroxylase, P450-C21, P450-C21B, P450c21, Progesterone 21-hydroxylase, Steroid 21-hydroxylase, steroid 21-hydroxylase system, steroid 21-hydroxylation system, steroid cytochrome P450 21-hydroxylase

ECTree

     1 Oxidoreductases
         1.14 Acting on paired donors, with incorporation or reduction of molecular oxygen
             1.14.14 With reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen into the other donor
                1.14.14.16 steroid 21-monooxygenase

Engineering

Engineering on EC 1.14.14.16 - steroid 21-monooxygenase

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PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
T241R
site-directed mutagenesis, the mutant shows improved solubility properties compared to the wild-type enzyme
T241R/L442A
site-directed mutagenesis, the mutant shows greatly improved solubility properties compared to the wild-type enzyme
A15T
-
natural mutation found in patients with classical congenital adrenal hyperplasia, no significant difference in activity compared to wild-type
A265C
naturally occuring mutation, the mutation causes side-chain steric clashes with the neighboring residues
A265V
A391T
naturally occuring mutation, the mutation disrupts the hydrophobicity of the region
A434V
naturally occuring mutation, the mutation causes steric clashes with the heme rendering the enzyme almost inactive
C169R
naturally occuring mutation, the mutation alters the region's hydrophobicity, conserved residue C169 makes hydrophobic interactions with the loop between E-F helices and F-helix
D322G
D407N
naturally occuring mutation, the mutation prevents salt bridge formation resulting in a localized, as opposed to global, destabilization of tertiary structure
E320K
naturally occuring mutation, the mutation of E320, which is a highly conserved residue on a negatively charged Glu-Glu-Leu-Asp (EELD) motif, alters the charge on the motif
E351K
-
rare missense mutation located in the ERR triad and found in a patient with virilizing congenital hyperplasia. Residual activity is about 1% of wild-type for both 17-hydroxyprogesterone and progesterone
E431K
naturally occuring mutation, the mutation prevents salt bridge formation resulting in a localized, as opposed to global, destabilization of tertiary structure
F404S
naturally occuring mutation, the mutation prevents stable packing interactions resulting in salt-wasting congenital adrenal hyperplasia
G178A
naturally occuring mutation, the mutation causes reduced structural flexibility of the sharp fold between the E- and F-helices
G291C
naturally occuring mutation, the mutation abolishes substrate binding causing salt-wasting congenital adrenal hyperplasia
G291R
naturally occuring mutation, the mutation abolishes substrate binding causing salt-wasting congenital adrenal hyperplasia
G291S
naturally occuring mutation, the mutation abolishes substrate binding causing salt-wasting congenital adrenal hyperplasia
G292C
0.32% of wild-type efficiency with substrate progesterone
G292D
naturally occuring mutation, the mutation abolishes substrate binding causing salt-wasting congenital adrenal hyperplasia
G292S
0.0005% of wild-type efficiency with substrate progesterone
G424S
naturally occuring mutation, the mutation imparts rigidity to the loop between K'- and L-helix
G56R
naturally occuring mutation, P57 and G56 form the hinge between the membrane interacting N-terminus and rest of the protein. The substitution of G56 with a polar and rigid Arg residue disrupts the hinge affecting the interactions of CYP21A2 with the membrane
G90V
naturally occuring mutation, mutation of G90 to valine affects the ability of R91 to hydrogen bond with heme, causing salt-wasting congenital adrenal hyperplasia
H119R
naturally occuring mutation, the mutation causes side-chain steric clashes with the neighboring residues
H365W
-
the naturally occuring CYP21A2 mutant exhibits minimal 21-hydroxylase activity to convert 17-hydroxyprogesterone to 11-deoxycortisol or progesterone to 11-deoxycorticosterone compared to the wild-type
H365Y
H365Y/R356W
H62L
naturally occuring mutation, the mutation may disrupt hydrogen bonding to reduce, but not eliminate, enzyme activity
I171N
-
mutation identified in Italian patient with congenital adrenal hyperplasia, less than 1% of wild-type enzyme activity
I172N
I194N
naturally occuring mutation, the mutation causes side-chain steric clashes with the neighboring residues
I230T
naturally occuring mutation, the mutation causes side-chain steric clashes with the neighboring residues
I236N/V237E/M239K
-
naturally occuring mutant, no enzymic activity, dominant negative effect over wild-type with 35% decrease in activity
I471A
site-directed mutagenesis, the mutant shows activity similar to the wild-type enzyme
I471G
site-directed mutagenesis, the mutant shows activity similar to the wild-type enzyme
I77T
naturally occuring mutation, the mutation disrupts the hydrophobic environment
K121Q
naturally occuring mutation, the mutation impairs the interaction with the P450 oxidoreductase
K122Q
-
missense mutation causing nonclassical 21-hydroxylase deficiency, shows reduced activity of 14% for the conversion of 17alpha-hydroxyprogesterone and 19% for the conversion of progesterone compared to wild type
L107R
naturally occuring mutation, the mutation abolishes heme binding and causes salt-wasting congenital adrenal hyperplasia
L107X
site-directed mutagenesis, inactive mutant
L108R
0.0003% of wild-type efficiency with substrate progesterone
L109X
site-directed mutagenesis, inactive mutant
L142P
naturally occuring mutation, the mutation of the D-helix causes helical disruption and destabilization of secondary structures
L166P
naturally occuring mutation, the mutation of the E-helix causes helical disruption and destabilization of secondary structures
L167P
naturally occuring mutation, the mutation of the E-helix causes helical disruption and destabilization of secondary structures
L236N/V237E/M239K
the mutation is associated with congenital adrenal hyperplasia
L261P
naturally occuring mutation, the mutation of the H-helix causes helical disruption and destabilization of secondary structures
L300F
naturally occuring mutation, the mutation causes localized destabilization of secondary structure
L307M
naturally occuring mutation, the mutation disrupts the optimal packing of side chains but does not alter the hydrophobic environment
L307V
naturally occuring mutation, the mutation disrupts the optimal packing of side chains but does not alter the hydrophobic environment
L308F
naturally occuring mutation, the mutation causes localized destabilization of secondary structure
L353R
naturally occuring mutation, the mutation abolishes heme binding and causes salt-wasting congenital adrenal hyperplasia
L363W
naturally occuring mutation, the mutation causes steric clashes with the heme rendering the enzyme almost inactive
L446P
N387K
naturally occuring mutation, the mutation causes side-chain steric clashes with the neighboring residues
P30E
naturally occuring mutation causing disruption of the interaction between the carbon of P30 in the N-terminal loop and the side chain of Y376 within the beta5-beta6 hairpin loop resuting in the salt-wasting disease
P31L
2.4% of wild-type efficiency with substrate progesterone
P31Q
0.0001% of wild-type efficiency with substrate progesterone
P432L
naturally occuring mutation, the mutation makes the structure more flexible and prevents cysteine from being presented to heme
P453S
P459H
naturally occuring mutation, the mutation disrupts the hydrophobicity of the region
P463L
naturally occuring mutation, the mutation interferes with the conformation of the beta8-beta9 loop with the subsequent closure of substrate entrance channel
P482S
-
natural mutation found in patients with nonclassical congenital adrenal hyperplasia, precocious pubarche, menstrual irregularities or hypertrichosis, about 70% of activity compared to wild-type
Q318X
the mutation is associated with congenital adrenal hyperplasia
Q481P
naturally occuring mutation, the mutation destabilizes the structure rendering the protein inactive
R124H
naturally occuring mutation, the mutation causes side-chain steric clashes with the neighboring residues
R132C
naturally occuring mutation, the mutation impairs the interaction with the P450 oxidoreductase
R149C
naturally occuring mutation, the mutation prevents salt bridge formation resulting in a localized, as opposed to global, destabilization of tertiary structure
R233G
naturally occuring mutation, the mutation may prevent R233 from binding to the 3-keto oxygen of the proximal 17OHP in the proper orientation, it does not influence protein activity significantly, resulting in minimal phenotype
R233K
naturally occuring mutation, the mutation may prevent R233 from binding to the 3-keto oxygen of the proximal 17OHP in the proper orientation, it does not influence protein activity significantly, resulting in minimal phenotype
R339H
naturally occuring mutation, the mutation impairs the interaction with the P450 oxidoreductase
R341P
R341W
naturally occuring mutation, the mutation impairs the interaction with the P450 oxidoreductase
R356P
naturally occuring mutation, the mutation disrupts the interaction of R356 with Q389 rendering the enzyme inactive and causing salt-wasting congenital adrenal hyperplasia
R356W
R357W
0.01% of wild-type efficiency with substrate progesterone
R369Q
naturally occuring mutation, the mutation impairs the interaction with the P450 oxidoreductase
R408C/L
naturally occuring mutation, the mutation destabilizes structural elements because of the extensive loss of hydrogen bonds
R408H
naturally occuring mutation, the mutation prevents normal hydrogen bonding with E351 and R354
R409C
0.4% of wild-type efficiency with substrate progesterone
R426C
naturally occuring mutation, the mutation disrupts the interaction of residues R91 and R426 rendering the protein nonfunctional and causing salt-wasting congenital adrenal hyperplasia
R426H
-
mutation identified in Italian patient with congenital adrenal hyperplasia, less than 1% of wild-type enzyme activity
R435C
naturally occuring mutation, the mutation prevents salt bridge formation resulting in a localized, as opposed to global, destabilization of tertiary structure
R479L
naturally occuring mutation, the mutation prevents salt bridge formation resulting in a localized, as opposed to global, destabilization of tertiary structure
R483P
naturally occuring mutation, the mutation prevents salt bridge formation resulting in a localized, as opposed to global, destabilization of tertiary structure
R483Q
S301Y
naturally occuring mutation, the mutation causes side-chain steric clashes with the neighboring residues
T168N
naturally occuring mutation, the mutation causes side-chain steric clashes with the neighboring residues
T295X
naturally occuring mutation, the mutation abolishes substrate binding and causes salt-wasting congenital adrenal hyperplasia
T296N
T450P
naturally occuring mutation, the mutation reduces flexibility of beta8-sheet, which helps stabilize the very long C-terminal loop
V139E
naturally occuring mutation, mutation to glutamate disrupts the interaction with residues V440 and L436 on the L-helix causing instability of the enzyme, charge repulsions between the side chain of mutated V139E and E437 of the E-helix render the protein unstable and inactive causing salt-wasting congenital adrenal hyperplasia
V249A
naturally occuring mutation, the mutation causes side-chain steric clashes with the neighboring residues
V281G
naturally occuring mutation, the mutation causes a loss of the hydrophobic pocket
V281L
V282L
2% of wild-type efficiency with substrate progesterone
V304M
naturally occuring mutation, the mutation causes side-chain steric clashes with the neighboring residues
V359A
V359G
site-directed mutagenesis, the mutant shows 10% reduced activity compared to the wild-type enzyme
V470A
site-directed mutagenesis, the mutant shows activity similar to the wild-type enzyme
V470A/I471A
site-directed mutagenesis, the mutant shows activity similar to the wild-type enzyme
V470G
site-directed mutagenesis, the mutant shows activity similar to the wild-type enzyme
W302R
naturally occuring mutation, the mutation prevents stable packing interactions resulting in salt-wasting congenital adrenal hyperplasia
W302S
W303R
0.0001% of wild-type efficiency with substrate progesterone
Y47C
naturally occuring mutation, the mutation disables hydrogen bonding with H38, the interaction is compensated by a weak His-Cys interaction
Y47L
naturally occuring mutation, the mutation disrupts hydrogen bonds and causes salt-wasting congenital adrenal hyperplasia
Y59N
naturally occuring mutation, the mutation disrupts the hydrophobicity of the region resulting in loss of function
additional information