EC Number   |
General Information |
Reference |
|---|
    1.3.99.4 | physiological function |
3-ketosteroid DELTA1-dehydrogenase (KsdD) is the key enzyme responsible for DELTA1-dehydrogenation, which is one of the most valuable reactions for steroid catabolism, roles of the putative KsdD homologues in DELTA1-dehydrogenation |
-, 763180 |
| 1.3.99.4 | physiological function |
3-ketosteroid DELTA1-dehydrogenase plays a crucial role in the early steps of steroid degradation by introducing a double bond between the C1 and C2 atoms of the A-ring of its 3-ketosteroid substrates |
-, 723868 |
| 1.3.99.4 | physiological function |
3-ketosteroid-DELTA1-dehydrogenase (KstD) catalyzes DELTA1-dehydrogenation and is involved in the steroid catabolism |
-, 762659 |
| 1.3.99.4 | physiological function |
3-oxosteroid DELTA1-dehydrogenases (DELTA1-KSTDs) are FAD-dependent enzymes that catalyze the introduction of a double bond between the C1 and C2 atoms of the A-ring of 3-ketosteroid substrates. They play a critical role in the early steps of the degradation of the steroid core. Enzyme DELTA1-KSTD is also essential for steroid ring opening under anaerobic conditions |
763443 |
| 1.3.99.4 | evolution |
3-oxosteroid DELTA1-dehydrogenases are found in a large variety of microorganisms, especially in bacteria belonging to the phylum Actinobacteria |
763443 |
| 1.3.99.4 | physiological function |
aerobic degradation of the sterol tetracyclic nucleus by microorganisms comprises the catabolism of A/B-rings, followed by that of C/D-rings. B-ring rupture at the C9,10-position is a key step involving 3-ketosteroid DELTA1-dehydrogenase (KstD) and 3-ketosteroid 9alpha-hydroxylase (KstH). Their activities lead to the aromatization of C4,5-en-containing A-ring causing the rupture of B-ring. C4,5alpha-hydrogenated 3-ketosteroid can be produced by the growing microorganism containing a 5alpha-reductase. In this case, the microorganism synthesizes, in addition to KstD and KstH, a 3-ketosteroid DELTA4-(5alpha)-dehydrogenase (Kst4D) in order to produce the A-ring aromatization, and consequently B-ring rupture. KstD and Kst4D are FAD-dependent oxidoreductases. KstH is composed of a reductase and a monooxygenase. This last component is the catalytic unit, it contains a Rieske-[2Fe-2S] center with a non-heme mononuclear iron in the active site. The characterized KstDs are active on 3-ketosteroids containing a short C17-chain or devoid of this chain. C-4,5-hydrogenated 3-ketosteroids are substrates, only if they are of the 5alpha-configuration. The DELTA1-dehydrogenation of 3-keto-4-en-steroid with KstD, purified from Nocardia corallina, is stimulated by molecular oxygen with stoichiometric production of hydrogen peroxide and 3-keto-1,4-diene-steroid. In addition, the purified KstD catalyzes hydrogen transfer from 3-keto-4-ene-steroid (donor) into 3-keto-1,4-dienesteroid (acceptor), e.g. progesterone to 1,4-androstadiene-3,17-dione (ADD). The purified KstD of N. corallina catalyzes efficiently the aromatization of A-ring of 19-nortestosterone and 19-norandrostenedione to produce respectively beta-estradiol and estrone (phenolic compounds). Also, 19-hydroxytestosterone, 19-hydroxyandrostenedione, and 19-oxotestosterone are reported to be substrates for this KstD. Their dehydrogenation produces the respective phenolic steroids. This steroid A-ring aromatization with the isolated KstD is similar to an earlier bioconversion, carried out using microbial cultures on 19-hydroxy-4-stene-3-one. The process of this bioconversion consists of the 19-hydroxystenone side chain cleavage first and second, the A-ring aromatization of the steroid derivative, producing beta-estradiol and/or estrone. Microbial 9alpha-hydroxylation does not occur in the process, due to the C19-hydroxyl group steric hindrance |
-, 763042 |
| 1.3.99.4 | malfunction |
all ksdD-overexpressing strains (isozymes KsdD1-5) not only exhibit a faster initial conversion rate (increased by 22-102%) but also achieve a higher conversion ratio (increased by 15-66%) than that of the control strain during the conversion of 4-androstene-3,17-dione to 1,4-androstadiene-3,17-dione. Apparently, KsdD3 and KsdD2 have more effect on DELTA1-dehydrogenation |
-, 763180 |
| 1.3.99.4 | malfunction |
an enzyme-deficient mutant strain is unable to use cholesterol as a source of carbon and energy and has a limited ability to multiply. The mutant is unable to inhibit the NO and reactive oxygen species production induced through Toll-like receptor 2 signaling in infected resting macrophages, phenotpe, overview |
-, 724670 |
| 1.3.99.4 | more |
enzyme residues Y125, Y365, and Y541 are essential to the function of KsdD, residues Y122, S138, and E140 contribute to the catalysis of KsdD, modelling of the enzyme-substrate bindung structure, overview |
-, 763772 |
| 1.3.99.4 | more |
homology-based structural analysis and structure modeling of KstD2 using the structure of SQ1-KstD1 Rhodococcus erythropolis SQ1 (PDB ID 4C3Y). Enzyme KstD1 and KstD2 belongs to clusters 1 and 2, respectively |
-, 762659 |
