steroid isomerases

Summary

Summary: Enzymes that catalyze the transposition of double bond(s) in a steroid molecule. EC 5.3.3.

Top Publications

  1. Mazumder D, Kahn K, Bruice T. Computational study of ketosteroid isomerase: insights from molecular dynamics simulation of enzyme bound substrate and intermediate. J Am Chem Soc. 2003;125:7553-61 pubmed
    ..S structures. This free movement of water disappears in the E. In structures. The active site is shielded by hydrophobic residues, which come together and squeeze out the waters from the active site in the E. In complex. ..
  2. Kraut D, Sigala P, Fenn T, Herschlag D. Dissecting the paradoxical effects of hydrogen bond mutations in the ketosteroid isomerase oxyanion hole. Proc Natl Acad Sci U S A. 2010;107:1960-5 pubmed publisher
    ..These results underscore the complex energetics of hydrogen bonding interactions and site-directed mutagenesis experiments. ..
  3. Cho H, Ha N, Choi G, Kim H, Lee D, Oh K, et al. Crystal structure of delta(5)-3-ketosteroid isomerase from Pseudomonas testosteroni in complex with equilenin settles the correct hydrogen bonding scheme for transition state stabilization. J Biol Chem. 1999;274:32863-8 pubmed
    ..Proton nuclear magnetic resonance analyses of several mutant enzymes indicate that the Tyr(14) OH forms a low barrier hydrogen bond with the dienolic oxyanion of the intermediate. ..
  4. Nam G, Cha S, Yun Y, Oh Y, Hong B, Lee H, et al. The conserved cis-Pro39 residue plays a crucial role in the proper positioning of the catalytic base Asp38 in ketosteroid isomerase from Comamonas testosteroni. Biochem J. 2003;375:297-305 pubmed
    ..Taken together, our results demonstrate that the conserved cis-Pro39 residue plays a crucial role in the proper positioning of the critical catalytic base Asp38 and in the structural integrity of the active site in KSI...
  5. Chakravorty D, Hammes Schiffer S. Impact of mutation on proton transfer reactions in ketosteroid isomerase: insights from molecular dynamics simulations. J Am Chem Soc. 2010;132:7549-55 pubmed publisher
    ..Moreover, small conformational changes due to stochastic thermal motions are required within this preorganized active site to facilitate the proton transfer reactions. ..
  6. Choi G, Ha N, Kim M, Hong B, Oh B, Choi K. Pseudoreversion of the catalytic activity of Y14F by the additional substitution(s) of tyrosine with phenylalanine in the hydrogen bond network of delta 5-3-ketosteroid isomerase from Pseudomonas putida biotype B. Biochemistry. 2001;40:6828-35 pubmed
  7. Park H, Merz K. Molecular dynamics and quantum chemical studies on the catalytic mechanism of Delta5-3-ketosteroid isomerase: the catalytic diad versus the cooperative hydrogen bond mechanism. J Am Chem Soc. 2003;125:901-11 pubmed
    ..This hypothesis is supported by the ab initio calculations which indicate that the CH intermediate is more stable than the CD one by approximately 6.3 kcal/mol. ..
  8. Petrounia I, Blotny G, Pollack R. Binding of 2-naphthols to D38E mutants of 3-oxo-Delta 5-steroid isomerase: variation of ligand ionization state with the nature of the electrophilic component. Biochemistry. 2000;39:110-6 pubmed
    ..Removal of either one of these H-bond donors (Tyr-14 or Asp-99) causes destabilization of the anion and results in a dienol enzyme-intermediate complex rather than a dienolate...
  9. Kim D, Nam G, Jang D, Choi G, Joo S, Kim J, et al. Roles of active site aromatic residues in catalysis by ketosteroid isomerase from Pseudomonas putida biotype B. Biochemistry. 1999;38:13810-9 pubmed
    ..Taken together, our results demonstrate that Phe-54, Phe-82, and Trp-116 contribute differentially to the stabilization of steroid species including substrate, intermediate, and product. ..

More Information

Publications95

  1. Pollack R, Thornburg L, Wu Z, Summers M. Mechanistic insights from the three-dimensional structure of 3-oxo-Delta(5)-steroid isomerase. Arch Biochem Biophys. 1999;370:9-15 pubmed
    ..In support of this hypothesis, effects on the kinetic parameters of the mutations Y14F and D99A are additive in the Y14F/D99A mutant...
  2. Kim S, Cha S, Cho H, Kim J, Ha N, Cho M, et al. High-resolution crystal structures of delta5-3-ketosteroid isomerase with and without a reaction intermediate analogue. Biochemistry. 1997;36:14030-6 pubmed
    ..1 kcal/mol), along with a moderate strength hydrogen bond of Asp99 ( approximately 4 kcal/mol), accounts for the required energy of 11 kcal/mol for the transition-state stabilization. ..
  3. Schwans J, Sunden F, Gonzalez A, Tsai Y, Herschlag D. Evaluating the catalytic contribution from the oxyanion hole in ketosteroid isomerase. J Am Chem Soc. 2011;133:20052-5 pubmed publisher
  4. Kamerlin S, Sharma P, Chu Z, Warshel A. Ketosteroid isomerase provides further support for the idea that enzymes work by electrostatic preorganization. Proc Natl Acad Sci U S A. 2010;107:4075-80 pubmed publisher
    ..We also clarify the crucial importance of having a well-defined physical concept when examining catalytic effects and the need for quantitative tools for analyzing such effects. ..
  5. Pollack R. Enzymatic mechanisms for catalysis of enolization: ketosteroid isomerase. Bioorg Chem. 2004;32:341-53 pubmed
    ..In this review, the mechanism of KSI is discussed, with particular emphasis on energetic considerations. Both experimental and theoretical approaches are considered to explain the mechanistic details of the reaction. ..
  6. Warshel A, Sharma P, Chu Z, Aqvist J. Electrostatic contributions to binding of transition state analogues can be very different from the corresponding contributions to catalysis: phenolates binding to the oxyanion hole of ketosteroid isomerase. Biochemistry. 2007;46:1466-76 pubmed
    ..It seems to us that this work provides an excellent example of the need for computational studies in analyzing key experimental findings about enzyme catalysis. ..
  7. Hanoian P, Hammes Schiffer S. Water in the active site of ketosteroid isomerase. Biochemistry. 2011;50:6689-700 pubmed publisher
  8. Chakravorty D, Soudackov A, Hammes Schiffer S. Hybrid quantum/classical molecular dynamics simulations of the proton transfer reactions catalyzed by ketosteroid isomerase: analysis of hydrogen bonding, conformational motions, and electrostatics. Biochemistry. 2009;48:10608-19 pubmed publisher
    ..Moreover, the conformational and electrostatic changes associated with these reactions are not limited to the active site but rather extend throughout the entire enzyme. ..
  9. Hanoian P, Sigala P, Herschlag D, Hammes Schiffer S. Hydrogen bonding in the active site of ketosteroid isomerase: electronic inductive effects and hydrogen bond coupling. Biochemistry. 2010;49:10339-48 pubmed publisher
    ..These studies also provide experimentally testable predictions about the impact of mutating the distal tyrosine residues in this hydrogen bonding network on the NMR chemical shifts and electronic absorption spectra...
  10. Zeng B, Bounds P, Steiner R, Pollack R. Nature of the intermediate in the 3-oxo-delta 5-steroid isomerase reaction. Biochemistry. 1992;31:1521-8 pubmed
    ..5 when it is bound to KSI. Thus, the function of Tyr-14 as an electrophilic catalyst is likely the stabilization of the anion of the dienol by hydrogen bonding rather than by proton transfer. ..
  11. Perrin C, Nielson J. "Strong" hydrogen bonds in chemistry and biology. Annu Rev Phys Chem. 1997;48:511-44 pubmed
    ..Although it has been proposed that strong, short, low-barrier hydrogen bonds are important in enzymatic reactions, it is concluded that the evidence for them in small molecules and in biomolecules is inconclusive. ..
  12. Somarowthu S, Brodkin H, D Aquino J, Ringe D, Ondrechen M, Beuning P. A tale of two isomerases: compact versus extended active sites in ketosteroid isomerase and phosphoglucose isomerase. Biochemistry. 2011;50:9283-95 pubmed publisher
    ..The results of these experiments demonstrate that, as predicted, remote residues are very important in PGI catalysis but make only small contributions to catalysis in KSI. ..
  13. Choi G, Ha N, Kim S, Kim D, Park S, Oh B, et al. Asp-99 donates a hydrogen bond not to Tyr-14 but to the steroid directly in the catalytic mechanism of Delta 5-3-ketosteroid isomerase from Pseudomonas putida biotype B. Biochemistry. 2000;39:903-9 pubmed
    ..2.4 A, short enough for a hydrogen bond to be formed. Taken together, these results strongly support the idea that Asp-99 contributes to the catalysis by donating a hydrogen bond directly to the intermediate. ..
  14. Schwans J, Sunden F, LASSILA J, Gonzalez A, Tsai Y, Herschlag D. Use of anion-aromatic interactions to position the general base in the ketosteroid isomerase active site. Proc Natl Acad Sci U S A. 2013;110:11308-13 pubmed publisher
  15. Feierberg I, Aqvist J. The catalytic power of ketosteroid isomerase investigated by computer simulation. Biochemistry. 2002;41:15728-35 pubmed
    ..The existence of such a water molecule could explain how the enzyme manages to maintain a low pK(a) for the general base residue. ..
  16. Schwans J, Kraut D, Herschlag D. Determining the catalytic role of remote substrate binding interactions in ketosteroid isomerase. Proc Natl Acad Sci U S A. 2009;106:14271-5 pubmed publisher
    ..These results suggest that remote binding interactions contribute >5 kcal/mol to catalysis by KSI but that local rather than remote interactions dictate the catalytic contributions from KSI's general base and oxyanion hole. ..
  17. Ha N, Choi G, Choi K, Oh B. Structure and enzymology of Delta5-3-ketosteroid isomerase. Curr Opin Struct Biol. 2001;11:674-8 pubmed
  18. Pettersson P, Johansson A, Mannervik B. Transmutation of human glutathione transferase A2-2 with peroxidase activity into an efficient steroid isomerase. J Biol Chem. 2002;277:30019-22 pubmed
  19. Shimodaira M, Nakayama T, Sato I, Sato N, Izawa N, Mizutani Y, et al. Estrogen synthesis genes CYP19A1, HSD3B1, and HSD3B2 in hypertensive disorders of pregnancy. Endocrine. 2012;42:700-7 pubmed publisher
    ..017). These data suggest that the estrogen synthesis gene, CYP19A1 is associated with PE in the Japanese population. ..
  20. Bain P, Yoo M, Clarke T, Hammond S, Payne A. Multiple forms of mouse 3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4 isomerase and differential expression in gonads, adrenal glands, liver, and kidneys of both sexes. Proc Natl Acad Sci U S A. 1991;88:8870-4 pubmed
    ..The results demonstrate that the mouse liver is a significant site of 3 beta HSD activity and demonstrate the existence of multiple 3 beta HSD structural genes in the mouse. ..
  21. Liu X, Fu J, Yun Y, Yin Y, Ma Z. A sterol C-14 reductase encoded by FgERG24B is responsible for the intrinsic resistance of Fusarium graminearum to amine fungicides. Microbiology. 2011;157:1665-75 pubmed publisher
    ..These results indicate that FgERG24B controls the intrinsic resistance of F. graminearum to amines. The finding of this study provides new insights into amine resistance in filamentous fungi. ..
  22. Hutchinson M, Chase H. Intensified process for the purification of an enzyme from inclusion bodies using integrated expanded bed adsorption and refolding. Biotechnol Prog. 2006;22:1187-93 pubmed
    ..This process should be applicable for other polyhistidine tagged proteins and is likely to have the greatest benefit for proteins that tend to aggregate when refolded by dilution. ..
  23. Yam J, Jin D, So C, Chan L. Identification and characterization of EBP, a novel EEN binding protein that inhibits Ras signaling and is recruited into the nucleus by the MLL-EEN fusion protein. Blood. 2004;103:1445-53 pubmed
    ..Taken together, our findings suggest a new mechanism for MLL-EEN-mediated leukemogenesis in which MLL-EEN interferes with the Ras-suppressing activities of EBP through direct interaction. ..
  24. Pazzaglia U, Zarattini G, Donzelli C, Benetti A, Bondioni M, Groli C. The nature of cartilage stippling in chondrodysplasia punctata: histopathological study of Conradi-Hünermann syndrome. Fetal Pediatr Pathol. 2008;27:71-81 pubmed publisher
    ..These findings fit well with the radiographic observations of progressive regression of stippling with advancing age of the child and also give a morphological correlation...
  25. Hashimoto N, Yamanaka H, Mizushima T, Noguchi K. Increased expression of 3 beta-hydroxysteroid dehydrogenase mRNA in dorsal root ganglion neurons of adult rats following peripheral nerve injury. Neurosci Lett. 2003;340:45-8 pubmed
    ..Our results suggest that progesterone may have a role in the process against neuronal injury or in regeneration in the peripheral nervous system. ..
  26. Grebenok R, Ohnmeiss T, Yamamoto A, Huntley E, Galbraith D, Della Penna D. Isolation and characterization of an Arabidopsis thaliana C-8,7 sterol isomerase: functional and structural similarities to mammalian C-8,7 sterol isomerase/emopamil-binding protein. Plant Mol Biol. 1998;38:807-15 pubmed
    ..t.SI1. Structural and biochemical similarities between the A. thaliana C-8,7 sterol isomerase and the mammalian emopamil-binding protein (EBP) are discussed. ..
  27. Yun Y, Nam G, Kim Y, Oh B, Choi K. Small exterior hydrophobic cluster contributes to conformational stability and steroid binding in ketosteroid isomerase from Pseudomonas putida biotype B. FEBS J. 2005;272:1999-2011 pubmed
  28. Morice Picard F, Kostrzewa E, Wolf C, Benlian P, Taieb A, Lacombe D. Evidence of postzygotic mosaicism in a transmitted form of Conradi-Hunermann-Happle syndrome associated with a novel EBP mutation. Arch Dermatol. 2011;147:1073-6 pubmed publisher
    ..To our knowledge, we report the first molecular confirmation of postzygotic mosaicism on an ichthyosiform skin lesion in the mother of a girl with X-linked dominant chondrodysplasia punctata associated with a novel EBP mutation. ..
  29. Toyohara J, Sakata M, Ishiwata K. Re-evaluation of in vivo selectivity of [(11)C]SA4503 to ?(1) receptors in the brain: contributions of emopamil binding protein. Nucl Med Biol. 2012;39:1049-52 pubmed publisher
    ..On the other hand, the effects of the high-affinity EBP blockers tamoxifen and trifluoperazine were negligible. Our results confirmed the ?(1)-selective binding of [(11)C]SA4503 in the brain. ..
  30. Vidal H, Mondesert G, Galiegue S, Carrière D, Dupuy P, Carayon P, et al. Identification and pharmacological characterization of SRBP-2: a novel SR31747A-binding protein. Cancer Res. 2003;63:4809-18 pubmed
    ..These findings demonstrated that SRBP-2 represents an additional molecular target for SR31747A, which could help to understand the immunosuppressive and antiproliferative effects of the molecule. ..
  31. Zhang L, Wang H, Yang Y, Liu H, Zhang Q, Xiang Q, et al. NGF induces adult stem Leydig cells to proliferate and differentiate during Leydig cell regeneration. Biochem Biophys Res Commun. 2013;436:300-5 pubmed publisher
    ..The discovery of this effect of NGF on Leydig cells will provide useful information for developing new potential therapies for PADAM (Partial Androgen Deficiency in the Aging Male). ..
  32. Silve S, Leplatois P, Josse A, Dupuy P, Lanau C, Kaghad M, et al. The immunosuppressant SR 31747 blocks cell proliferation by inhibiting a steroid isomerase in Saccharomyces cerevisiae. Mol Cell Biol. 1996;16:2719-27 pubmed
    ..The results suggest that sterol isomerase is the target of SR 31747 and that both the SUR4 and FEN1 gene products are required to mediate the proliferation arrest induced by ergosterol depletion. ..
  33. Oliynyk M, Stark C, Bhatt A, Jones M, Hughes Thomas Z, Wilkinson C, et al. Analysis of the biosynthetic gene cluster for the polyether antibiotic monensin in Streptomyces cinnamonensis and evidence for the role of monB and monC genes in oxidative cyclization. Mol Microbiol. 2003;49:1179-90 pubmed
    ..coelicolor was shown to significantly increase the ability of S. coelicolor to epoxidize linalool, a model substrate for the presumed linear polyketide intermediate in monensin biosynthesis. ..
  34. Hénot F, Pollack R. Catalytic activity of the D38A mutant of 3-oxo-Delta 5-steroid isomerase: recruitment of aspartate-99 as the base. Biochemistry. 2000;39:3351-9 pubmed
    ..This mechanism is supported by the lack of detectable activity of the D38A/D99N, D38A/Y14F, and D38A/Y55F double mutants. ..
  35. Aughton D, Kelley R, Metzenberg A, Pureza V, Pauli R. X-linked dominant chondrodysplasia punctata (CDPX2) caused by single gene mosaicism in a male. Am J Med Genet A. 2003;116A:255-60 pubmed
    ..Biochemical and molecular studies demonstrate that he is mosaic for a sterol-delta(8)-delta(7) isomerase gene mutation. He is the first reported example of single gene mosaicism giving rise to CDPX2 in a male. ..
  36. Sato H, Feix J. Osmoprotection of bacterial cells from toxicity caused by antimicrobial hybrid peptide CM15. Biochemistry. 2006;45:9997-10007 pubmed
    ..These data indicate that the formation of discrete pores in the cytoplasmic membrane is a key factor in the mechanism of bacterial killing by CM15. ..
  37. Ibanez C, Guennoun R, Liere P, Eychenne B, Pianos A, El Etr M, et al. Developmental expression of genes involved in neurosteroidogenesis: 3beta-hydroxysteroid dehydrogenase/delta5-delta4 isomerase in the rat brain. Endocrinology. 2003;144:2902-11 pubmed
    ..These results demonstrate variations in the expression of a gene coding for an enzyme critically involved in progesterone synthesis in the hippocampus throughout postnatal development. ..
  38. Huber I, Wappl Kornherr E, Sinnegger Brauns M, Hoda J, Walter Bastl D, Striessnig J. Opposite effects of a single IIIS5 mutation on phenylalkylamine and dihydropyridine interaction with L-type Ca2+ channels. J Biol Chem. 2004;279:55211-7 pubmed
    ..Mutation of Thr-1066 to a non-L-type tyrosine residue can be exploited to differentially affect phenylalkylamine and dihydropyridine binding to L-type Ca(2+) channels. ..
  39. Huang C, Chao C, Shen M, Chen T, Li Y. Preparation of high-performance water-soluble quantum dots for biorecognition through fluorescence resonance energy transfer. Chem Asian J. 2012;7:2848-53 pubmed publisher
    ..With a ?(5)-3-ketosteroid isomerase adsorbed PDDA-QD complex, the biorecognition of steroids was demonstrated through the application of fluorescent resonance energy transfer. ..
  40. Arnold A, Bruckner Tuderman L, Has C, Happle R. Conradi-Hünermann-Happle syndrome in males vs. MEND syndrome (male EBP disorder with neurological defects). Br J Dermatol. 2012;166:1309-13 pubmed publisher
    ..Because the clinical outcome and prognosis are different it is important to distinguish between males with CHH syndrome that represents a mosaic phenotype, and those with MEND syndrome that is a nonmosaic trait. ..
  41. Murono E, Washburn A. Evidence that Leydig precursors localize in immature band two cells isolated on Percoll gradients. J Steroid Biochem Mol Biol. 1990;37:675-80 pubmed
    ..These results suggest that during a limited period of maturation precursor cells in Band 2, which are undetected by histochemical staining for 3 beta-HSD, can be converted to Leydig cells in culture by hCG. ..
  42. Jang D, Lee H, Lee B, Hong B, Cha H, Yoon J, et al. Detection of an intermediate during the unfolding process of the dimeric ketosteroid isomerase. FEBS Lett. 2006;580:4166-71 pubmed
    ..Taken together, our results suggest that the formation of a compact intermediate should precede the association of monomers prior to the dimerization process during the folding of KSI. ..
  43. Ikegawa S, Ohashi H, Ogata T, Honda A, Tsukahara M, Kubo T, et al. Novel and recurrent EBP mutations in X-linked dominant chondrodysplasia punctata. Am J Med Genet. 2000;94:300-5 pubmed
    ..X-inactivation patterns of the patients showed no skewing, an observation that supports the assumption that inactivation of the EBP gene occurs at random in affected individuals...
  44. Moebius F, Reiter R, Hanner M, Glossmann H. High affinity of sigma 1-binding sites for sterol isomerization inhibitors: evidence for a pharmacological relationship with the yeast sterol C8-C7 isomerase. Br J Pharmacol. 1997;121:1-6 pubmed
    ..Because of its affiliations with yeast and mammalian sterol isomerases we propose that the sigma 1-binding site is localized on a sterol isomerase related protein, involved in postsqualene sterol biosynthesis. ..
  45. Layfield J, Hammes Schiffer S. Calculation of vibrational shifts of nitrile probes in the active site of ketosteroid isomerase upon ligand binding. J Am Chem Soc. 2013;135:717-25 pubmed publisher
    ..This QM/MM methodology is applicable to a wide range of biological systems and has the potential to assist in the elucidation of the fundamental principles underlying enzyme catalysis. ..
  46. Liu S, Mao B, Bai Y, Liu J, Li H, Li X, et al. Effects of Methoxychlor and Its Metabolite Hydroxychlor on Human Placental 3?-Hydroxysteroid Dehydrogenase 1 and Aromatase in JEG-3 Cells. Pharmacology. 2016;97:126-33 pubmed publisher
    ..When testosterone was used, HPTE was a mixed inhibitor of CYP19A1. In conclusion, MXC and HPTE are potent inhibitors of human HSD3B1, and HPTE is a weak CYP19A1 inhibitor. ..
  47. Hammes Schiffer S. Catalytic efficiency of enzymes: a theoretical analysis. Biochemistry. 2013;52:2012-20 pubmed publisher
  48. von Teichman A, Joerg H, Werner P, Brenig B, Stranzinger G. cDNA cloning and physical mapping of porcine 3 beta-hydroxysteroid dehydrogenase/Delta 5-Delta 4 isomerase. Anim Genet. 2001;32:298-302 pubmed
    ..Fluorescence in situ hybridization (FISH) was performed with a labelled PAC clone containing the gene of interest. The 3 beta-HSD gene was mapped to the porcine chromosome 4q16-4q21 which is in accordance with the comparative gene map. ..
  49. Lorence M, Murry B, Trant J, Mason J. Human 3 beta-hydroxysteroid dehydrogenase/delta 5----4isomerase from placenta: expression in nonsteroidogenic cells of a protein that catalyzes the dehydrogenation/isomerization of C21 and C19 steroids. Endocrinology. 1990;126:2493-8 pubmed
    ..Thus, the dehydrogenation/isomerization steps of steroid biosynthesis can be catalyzed by a single polypeptide chain, which can metabolize all of the major physiological substrates. ..
  50. Ying F, Ding C, Ge R, Wang X, Li F, Zhang Y, et al. Comparative evaluation of nonylphenol isomers on steroidogenesis of rat Leydig Cells. Toxicol In Vitro. 2012;26:1114-21 pubmed publisher
  51. Durocher F, Sanchez R, Ricketts M, Labrie Y, Laudet V, Simard J. Characterization of the guinea pig 3beta-hydroxysteroid dehydrogenase/Delta5-Delta4-isomerase expressed in the adrenal gland and gonads. J Steroid Biochem Mol Biol. 2005;97:289-98 pubmed
  52. Happle R. Hypomorphic alleles within the EBP gene cause a phenotype quite different from Conradi-Hünermann-Happle syndrome. Am J Med Genet A. 2003;122A:279; author reply 280 pubmed
  53. Milunsky J, Maher T, Metzenberg A. Molecular, biochemical, and phenotypic analysis of a hemizygous male with a severe atypical phenotype for X-linked dominant Conradi-Hunermann-Happle syndrome and a mutation in EBP. Am J Med Genet A. 2003;116A:249-54 pubmed
    ..The mild maternal phenotype has been described previously. However, this nonmosaic missense mutation has resulted in a severe phenotype in her surviving son...
  54. Park T, Choi S, Gang G, Kim Y. High-level expression and purification of the second transmembrane domain of wild-type and mutant human melanocortin-4 receptor for solid-state NMR structural studies. Protein Expr Purif. 2008;62:139-45 pubmed publisher
  55. Bravo Moreno J, Diaz Sanchez V, Montoya Flores J, Lamoyi E, Saez J, Pérez Armendariz E. Expression of connexin43 in mouse Leydig, Sertoli, and germinal cells at different stages of postnatal development. Anat Rec. 2001;264:13-24 pubmed
    ..We also provide evidence for the first time that Cx43-gap junctions communicate between Sertoli and germinal cells before and during the first wave of spermatogenesis. ..
  56. Jin Y, Kuznetsova T, Citterio L, Thijs L, Messaggio E, Casamassima N, et al. Left ventricular structure and function in relation to steroid biosynthesis genes in a white population. Am J Hypertens. 2012;25:986-93 pubmed publisher
    ..07). Pending confirmation in other studies, LV mass and LV diastolic function seem to be related to genetic variation in the steroid biosynthesis. ..
  57. Horinouchi M, Hayashi T, Kudo T. Steroid degradation in Comamonas testosteroni. J Steroid Biochem Mol Biol. 2012;129:4-14 pubmed publisher
    ..testosteroni. Article from a special issue on steroids and microorganisms...
  58. Rutherfurd K, Chen S, Shively J. Isolation and amino acid sequence analysis of bovine adrenal 3 beta-hydroxysteroid dehydrogenase/steroid isomerase. Biochemistry. 1991;30:8108-16 pubmed
  59. Cherney M, Garen C, James M. Crystal structure of Mycobacterium tuberculosis Rv0760c at 1.50 A resolution, a structural homolog of Delta(5)-3-ketosteroid isomerase. Biochim Biophys Acta. 2008;1784:1625-32 pubmed publisher
    ..The structures of native Rv0760c in several different crystal forms and Rv0760c bound to 17beta-estradiol 17-hemisuccinate (EH) have also been solved and analyzed. ..
  60. Lee H, Yoon Y, Jang D, Kim C, Cha H, Hong B, et al. 15N NMR relaxation studies of Y14F mutant of ketosteroid isomerase: the influence of mutation on backbone mobility. J Biochem. 2008;144:159-66 pubmed publisher
    ..The results thus suggest that the hydrogen bond network in the active site might be disrupted by the Y14F mutation, resulting in a loss of the direct interactions between the catalytic residues and 19-NTHS...
  61. Bourrie B, Bribes E, De Nys N, Esclangon M, Garcia L, Galiegue S, et al. SSR125329A, a high affinity sigma receptor ligand with potent anti-inflammatory properties. Eur J Pharmacol. 2002;456:123-31 pubmed
    ..The results of this study provide substantial evidence that sigma receptor ligands may represent a new effective approach for rheumatoid arthritis treatment. ..
  62. Kraut D, Sigala P, Pybus B, Liu C, Ringe D, Petsko G, et al. Testing electrostatic complementarity in enzyme catalysis: hydrogen bonding in the ketosteroid isomerase oxyanion hole. PLoS Biol. 2006;4:e99 pubmed
  63. Zhao H, Simard J, Labrie C, Breton N, Rheaume E, Luu The V, et al. Molecular cloning, cDNA structure and predicted amino acid sequence of bovine 3 beta-hydroxy-5-ene steroid dehydrogenase/delta 5-delta 4 isomerase. FEBS Lett. 1989;259:153-7 pubmed
    ..Hybridization of cloned cDNAs to bovine ovary poly(A)+ RNA shows the presence of an approximately 1.7 kb mRNA species. ..
  64. Schwans J, Hanoian P, Lengerich B, Sunden F, Gonzalez A, Tsai Y, et al. Experimental and computational mutagenesis to investigate the positioning of a general base within an enzyme active site. Biochemistry. 2014;53:2541-55 pubmed publisher
  65. Cañueto J, Giros M, Gonzalez Sarmiento R. The role of the abnormalities in the distal pathway of cholesterol biosynthesis in the Conradi-Hünermann-Happle syndrome. Biochim Biophys Acta. 2014;1841:336-44 pubmed publisher
    ..This article is part of a Special Issue entitled The Important Role of Lipids in the Epidermis and their Role in the Formation and Maintenance of the Cutaneous Barrier. Guest Editors: Kenneth R. Feingold and Peter Elias. ..
  66. Sonda N, Simonato F, Peranzoni E, Calì B, Bortoluzzi S, Bisognin A, et al. miR-142-3p prevents macrophage differentiation during cancer-induced myelopoiesis. Immunity. 2013;38:1236-49 pubmed publisher
    ..By modulating a specific miR in bone marrow precursors, we thus demonstrated the feasibility of altering tumor-induced macrophage differentiation as a potent tool to improve the efficacy of cancer immunotherapy. ..
  67. Chou Y, Jeng Y, Mao T. HSD3B1 is a specific trophoblast-associated marker not expressed in a wide spectrum of tumors. Int J Gynecol Cancer. 2013;23:343-7 pubmed publisher
    ..Our study further confirmed that HSD3B1 is a highly specific trophoblast-associated marker that can be used in the distinction of trophoblastic tumorlike lesions and tumors from nontrophoblastic lesions and tumors. ..
  68. Soma K, Sinchak K, Lakhter A, Schlinger B, Micevych P. Neurosteroids and female reproduction: estrogen increases 3beta-HSD mRNA and activity in rat hypothalamus. Endocrinology. 2005;146:4386-90 pubmed
    ..These data support the hypothesis that PROG is a neurosteroid, produced locally in the hypothalamus from cholesterol, which functions in the estrogen positive-feedback mechanism driving the LH surge. ..
  69. Hartman R, Molho Pessach V, Schaffer J. Conradi-Hünermann-Happle syndrome. Dermatol Online J. 2010;16:4 pubmed
    ..This reports highlights the evolution of clinical findings over time in this X-linked dominant form of chondrodysplasia punctata. ..
  70. Kostic T, Stojkov N, Bjelic M, Mihajlovic A, Janjic M, Andric S. Pharmacological doses of testosterone upregulated androgen receptor and 3-Beta-hydroxysteroid dehydrogenase/delta-5-delta-4 isomerase and impaired leydig cells steroidogenesis in adult rats. Toxicol Sci. 2011;121:397-407 pubmed publisher
    ..The upregulation of AR and 3?HSD in testosterone-impaired Leydig cells steroidogenesis could be the possible mechanism that maintain and prevent loss of steroidogenic function...
  71. Sharma K, Vázquez Ramírez R, Kubli Garfias C. A theoretical model of the catalytic mechanism of the Delta5-3-ketosteroid isomerase reaction. Steroids. 2006;71:549-57 pubmed
    ..The mechanism described herein accounts for all of the properties, as well as the flow of atomic charges, explaining both catalytic mechanism and proficiency of KSI. ..
  72. Childs W, Boxer S. Proton affinity of the oxyanion hole in the active site of ketosteroid isomerase. Biochemistry. 2010;49:2725-31 pubmed publisher
  73. Ruben E, Schwans J, Sonnett M, Natarajan A, Gonzalez A, Tsai Y, et al. Ground state destabilization from a positioned general base in the ketosteroid isomerase active site. Biochemistry. 2013;52:1074-81 pubmed publisher
    ..This ground state destabilization mechanism may be common to the many enzymes with anionic side chains that deprotonate carbon acids. ..
  74. Datta M, Nagendra Prasad R, Navneet A, Roy S, Bhattacharya S. Thyroid hormone-induced protein (TIP) gene expression by 3,5,3(')-triiodothyronine in the ovarian follicle of perch (Anabas testudineus, Bloch): modulation of 3beta-hydroxysteroid dehydrogenase/Delta(5)-Delta(4)-isomerase enzyme by TIP. Gen Comp Endocrinol. 2002;126:334-41 pubmed
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