1.1.1.184: carbonyl reductase (NADPH)

This is an abbreviated version, for detailed information about carbonyl reductase (NADPH), go to the full flat file.

Reaction

R-CHOH-R'
+
NADP+
=
R-CO-R'
+
NADPH
+
H+

Synonyms

15-hydroxyprostaglandin dehydrogenase [NADP+], 2,5-diketo-D-gluconic acid reductase, Adipocyte P27 protein, aldehyde reductase 1, aldehyde reductase I, aldo-keto reductase, ALR3, AP27, carbonyl reductase, carbonyl reductase (NADPH), carbonyl reductase 1, carbonyl reductase 3, carbonyl reductase S1, CBR, CBR 1, CBR 3, CBR1, CBR3, CHCR, CHCR1, CHCR2, CHCR3, CR, CSCR1, Gox0644, Gox1615, ketoreductase, KLCR1, KR, LCR, microsomal carbonyl reductase, More, NADP+-dependent ADH, NADPH-carbonyl reductase, NADPH-dependent carbonyl reductase, NADPH-dependent carbonyl reductase S1, NCCR, nonspecific NADPH-dependent carbonyl reductase, peroxisomal-type carbonyl reductase, PHCR, prostaglandin 9-ketoreductase, Prostaglandin-E2 9-reductase, PTCR, R-specific carbonyl reductase, reductase S1, reductase, carbonyl, RLCR, SCR, SDR21C1, secondary-alcohol: NADP+-oxidoreductase, short-chain (S)-1-phenyl-1,2-ethanediol dehydrogenase, short-chain carbonyl reductase, sniffer, SSCR, Tm1743, Tm_1743, xenobiotic carbonyl reductase, xenobiotic ketone reductase, YtbE

ECTree

     1 Oxidoreductases
         1.1 Acting on the CH-OH group of donors
             1.1.1 With NAD+ or NADP+ as acceptor
                1.1.1.184 carbonyl reductase (NADPH)

Engineering

Engineering on EC 1.1.1.184 - carbonyl reductase (NADPH)

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ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
S41A/S42A/S43Q/W63I/Y64D/N65I/S66N
-
site-sirected mutagenesis, mutant S1M1 shows reduced activity and inverted cofactor specificity, using exclusively NADH, compared to the wild-type enzyme
S41A/S42A/S43R/W63I/Y64D/N65I/S66N
-
site-sirected mutagenesis, mutant S1M4 shows reduced activity and inverted cofactor specificity, using exclusively NADH, compared to the wild-type enzyme
S41A/S42A/S43Q/W63I/Y64D/N65I/S66N
-
site-sirected mutagenesis, mutant S1M1 shows reduced activity and inverted cofactor specificity, using exclusively NADH, compared to the wild-type enzyme
-
S41A/S42A/S43R/W63I/Y64D/N65I/S66N
-
site-sirected mutagenesis, mutant S1M4 shows reduced activity and inverted cofactor specificity, using exclusively NADH, compared to the wild-type enzyme
-
DELTA31
-
deletion of the N-terminal 31 residues, kinetic parameters KM and kcat are essentially the same as those of the wild-type. It forms a tetramer in solution, which is similar to the wild-type but is less stable. Melting temperature is 48C, which is lower than that of the wild-type (52C)
H68D
-
produces (R)-enantiomer with low optical purity and yield
H68D/P69D
-
produces (R)-enantiomer with low optical purity and yield
P69D
-
produces (R)-enantiomer with low optical purity and yield
S67D
-
produces (R)-enantiomer with low optical purity and yield
S67D/H68D
S67D/P69D
-
produces (R)-enantiomer with low optical purity and yield
H68D
-
produces (R)-enantiomer with low optical purity and yield
-
P69D
-
produces (R)-enantiomer with low optical purity and yield
-
S172A
-
melting temperature is 46C, which is lower than that of the wild-type (52C). Shows no activity
-
S172T
-
melting temperature is 48C, which is lower than that of the wild-type (52C). Activity is essentially the same as the wild-type
-
S67D
-
produces (R)-enantiomer with low optical purity and yield
-
S67D/H68D
-
double-point mutation inside the coenzyme-binding pocket results in a nearly 10fold increase and a 20fold decrease in the kcat/KM value when NADH and NADPH are used as cofactors, respectively, with kcat remaining essentially the same. Shows similar thermal stability to wild-type; produces (R)-1-phenyl-1,2-ethanediol with high optical purity of 95.4% and a yield of 83.1% in the NADH-linked reaction. It results in a nearly 10fold increase and a 20fold decrease in the kcat/Km value when NADH and NADPH are used as the cofactors, respectively, but maintaining a kcat value essentially the same with respect to wild-type. The mutant has a stronger preference for NADH and weaker binding for NADPH. It exhibits a secondary structure and melting temperature similar to the wild-type form. NADH provides maximal protection against thermal and urea denaturation for S67D/H68D, in contrast to the effective protection by NADP(H) for the wild-type enzyme. Thus, the double point mutation S67D/H68D successfully converts the coenzyme specificity of SCR from NADP(H) to NAD(H) as well as the product enantioselectivity without disturbing enzyme stability
-
S67D/P69D
-
produces (R)-enantiomer with low optical purity and yield
-
V270D
-
renders the SCR as a homodimer, rather than a tetramer, without affecting the enzymatic activity. Melting temperature is 45C, which is lower than that of the wild-type (52C)
-
Y187A
-
melting temperature is 45C, which is lower than that of the wild-type (52C). Shows no activity
-
W230P
-
exhibits properties similar to the parent enzyme with regard to steroid specificities and kinetics toward substrates
C227S
displays a similar kcat, but a 30fold higher Km value for S-nitrosoglutathione, and does not show substrate inhibition
D236A/K238P/D239K/S240A/I241T/R242K/T243S/V244P
mutations introduce activity towards S-nitrosoglutathione
P230W/D236A/K238P/D239K/S240A/I241T/R242K/T243S/V244P
mutations introduce activity towards S-nitrosoglutathione
Q142M/C143S/P230W/D236A/K238P/D239K/S240A/I241T/R242K/T243S/V244P/H270S
mutations introduce activity towards S-nitrosoglutathione
V88I
-
functional genetic polymorphism. Mutation results in CBR1 isoforms with different binding affinities for cofactor NADPH and inhibitor rutin as well as different maximal velocities for reaction with daunorubicin and prostaglandin E2
W230P
exhibits properties similar to the parent enzyme with regard to steroid specificities and kinetics toward substrates
Q245H
-
inversion of enantioselectivity from (R)- to (S)-configuration of reduced acetophenone product, with enhanced enantioselectivity
Q245L
-
inversion of enantioselectivity from (R)- to (S)-configuration of reduced acetophenone product, with enhanced enantioselectivity
Q245P
-
inversion of enantioselectivity from (R)- to (S)-configuration of reduced acetophenone product, with enhanced enantioselectivity
E142M
increase in reaction velocity
E142V
increase in reaction velocity
additional information