The DOI matches its Crossref record; 71 of the 71 references it cites were found in a registry or an index.
Molecular Modeling of Human P450c17 (17α-Hydroxylase/ 17,20-Lyase): Insights into Reaction Mechanisms and Effects of Mutations
Open accessAbstract
P450c17 (17alpha-hydroxylase/17,20-lyase) catalyzes steroid 17alpha-hydroxylase and 17,20-lyase activities in the biosynthesis of androgens and estrogens. These two activities are differentially regulated in a tissue-specific and developmentally programmed manner. To visualize the active site topology of human P450c17 and to study the structural basis of its substrate specificity and catalytic selectivity, we constructed a second-generation computer-graphic model of human P450c17. The energetics of the model are comparable to those of the principal template of the model, P450BMP, as determined from its crystallographic coordinates. The protein structure analysis programs PROCHECK, WHATIF, and SurVol indicate that the predicted P450c17 structure is reasonable. The hydrophobic active site accommodates both delta4 and delta5 steroid substrates in a catalytically favorable orientation. The predicted contributions of positively charged residues to the redox-partner binding site were confirmed by site-directed mutagenesis. Molecular dynamic simulations with pregnenolone, 17-OH-pregnenolone, progesterone, and 17-OH-progesterone docked into the substrate-binding pocket demonstrated that regioselectivity of the hydroxylation reactions is determined both by proximity of hydrogens to the iron-oxo complex and by the stability of the carbon radicals generated after hydrogen abstraction. The model explains the activities of all known naturally occurring and synthetic human P450c17 mutants. The model predicted that mutation of lysine 89 would disrupt 17,20-lyase activity to a greater extent than 17alpha-hydroxylase activity; expression of a test mutant, K89N, in yeast confirmed this prediction. Hydrogen peroxide did not support catalysis of the 17,20-lyase reaction, as would be predicted by mechanisms involving a ferryl peroxide. Our present model and biochemical data suggest that both the hydroxylase and lyase activities proceed from a common steroid-binding geometry by an iron oxene mechanism. This model will facilitate studies of sex steroid synthesis and its disorders and the design of specific inhibitors useful in chemotherapy of sex steroid-dependent cancers.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“The model identifies Arg 347 and Arg 358 and several other arginine and lysine residues in the redox partner binding site; mutations of these residues all cause varying degrees of selective loss of 17,20lyase activity (240, 279, 280, 284).”
From The Molecular Biology, Biochemistry, and Physiology of Human Steroidogenesis and Its Disorders (2011) · cites this paper as [240]
In the citing paper
“Computational modeling of P450c17 predicts the effects of all known mutations, including those with partial retention of both activities and those causing selective 17,20-lyase deficiency (240).”
From The Molecular Biology, Biochemistry, and Physiology of Human Steroidogenesis and Its Disorders (2011) · cites this paper as [240]
In the citing paper
“Basic residues in the redox-partner-binding surface of the recipient P450 are crucial for electron transfer from POR (49, 302), as shown by the mutations in human P450c17 that cause 17,20lyase deficiency (240, 280).”
From The Molecular Biology, Biochemistry, and Physiology of Human Steroidogenesis and Its Disorders (2011) · cites this paper as [240]
In the citing paper
“Genetic and biochemical studies have implicated basic residues in P450c17, including R347, R358, and perhaps R449 and K89, as important for its interaction with cytochrome b 5 (240,280,348), whereas E48 and E49 of cytochrome b 5 are required for high 17,20-lyase activity (349).”
From The Molecular Biology, Biochemistry, and Physiology of Human Steroidogenesis and Its Disorders (2011) · cites this paper as [240]
In the citing paper
“By analogy with the computationally inferred structure of P450c17 (240), Arg 356 appears to be part of the redox-partner-binding site, Val 281 appears to participate in coordinating the heme moiety, and Cys 428 is the crucial cystine residue in the hemebinding site found in all cytochrome P450 enzymes.”
From The Molecular Biology, Biochemistry, and Physiology of Human Steroidogenesis and Its Disorders (2011) · cites this paper as [240]
Citations
Cites
PROCHECK: a program to check the stereochemical quality of protein structures
Laskowski, R. A., MacArthur, M. W., Moss, D. S., & Thornton, J. M. (1993) · Journal of Applied Crystallography · doi:10.1107/s0021889892009944 · Cited by 24,581
A comprehensive set of sequence analysis programs for the VAX
Devereux, J., Haeberli, P. E., & Smithies, O. (1984) · Nucleic Acids Research · doi:10.1093/nar/12.1part1.387 · Cited by 14,222
Bayly, C. I., Cieplak, P., Cornell, W. D., & Kollman, P. A. (1993) · The Journal of Physical Chemistry · doi:10.1021/j100142a004 · Cited by 8,152
HIGH-RESOLUTION CRYSTAL STRUCTURE OF CYTOCHROME P450-CAM
Poulos, T. L., Finzel, B. C., & Howard, A. J. (1987) · Journal of Molecular Biology · doi:10.1016/0022-2836(87)90190-2 · Cited by 1,419
Molecular biology of steroid hormone synthesis
MILLER, W. L. (1988) · Endocrine Reviews · doi:10.1210/edrv-9-3-295 · Cited by 1,397
Self-citationORENTREICH, N., BRIND, J. L., RIZER, R. L., & VOGELMAN, J. H. (1984) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-59-3-551 · Cited by 1,349
An Evolutionary Trace Method Defines Binding Surfaces Common to Protein Families
Lichtarge, O., Bourne, H. R., & Cohen, F. E. (1996) · Journal of Molecular Biology · doi:10.1006/jmbi.1996.0167 · Cited by 1,196
Ferrin, T. E., Huang, C. C., Jarvis, L. E., & Langridge, R. (1988) · Journal of Molecular Graphics · doi:10.1016/0263-7855(88)80054-7 · Cited by 950
Crystal Structure of Hemoprotein Domain of P450BM-3, a Prototype for Microsomal P450's
Ravichandran, K. G., Boddupalli, S. S., Hasermann, C. A., Peterson, J. A., & Deisenhofer, J. (1993) · Science · doi:10.1126/science.8342039 · Cited by 879
Wang, M., Roberts, D. L., Paschke, R., Shea, T. M., Masters, B. S. S., & Kim, J.-J. P. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.16.8411 · Cited by 744
Flagged first, then by citations
Cited by
Sorted by citations
The Molecular Biology, Biochemistry, and Physiology of Human Steroidogenesis and Its Disorders
Miller, W. L., & Auchus, R. J. (2011) · Endocrine Reviews · doi:10.1210/er.2010-0013 · Cited by 2,458
Self-citationCongenital adrenal hyperplasia due to 21-hydroxylase deficiency*
White, P. C., & Speiser, P. W. (2000) · Endocrine Reviews · doi:10.1210/edrv.21.3.0398 · Cited by 1,432
Mutant P450 oxidoreductase causes disordered steroidogenesis with and without Antley-Bixler syndrome
Flück, C. E., Tajima, T., Pandey, A. V., Arlt, W., Okuhara, K., Verge, C. F., Jabs, E. W., Mendonça, B. B., Fujieda, K., & Miller, W. L. (2004) · Nature Genetics · doi:10.1038/ng1300 · Cited by 509
Self-citationThe backdoor pathway to dihydrotestosterone
Auchus, R. J. (2004) · Trends in Endocrinology & Metabolism · doi:10.1016/j.tem.2004.09.004 · Cited by 347
Self-citationHuang, N., Pandey, A. V., Agrawal, V., Reardon, W., Lapunzina, P. D., Mowat, D., Jabs, E. W., Vliet, G. V., Sack, J., Flück, C. E., et al. (2005) · The American Journal of Human Genetics · doi:10.1086/429417 · Cited by 336
Self-citationMinireview: Regulation of Steroidogenesis by Electron Transfer
Miller, W. L. (2005) · Endocrinology · doi:10.1210/en.2005-0096 · Cited by 324
Self-citationFormation and Cleavage of C–C Bonds by Enzymatic Oxidation–Reduction Reactions
Guengerich, F. P., & Yoshimoto, F. K. (2018) · Chemical Reviews · doi:10.1021/acs.chemrev.8b00031 · Cited by 298
NADPH P450 oxidoreductase: Structure, function, and pathology of diseases
Pandey, A. V., & Flück, C. E. (2013) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2013.01.010 · Cited by 279
THE GENETICS, PATHOPHYSIOLOGX, AND MANAGEMENT OF HUMAN DEFICIENCIES OF P450c17
Auchus, R. J. (2001) · Endocrinology and Metabolism Clinics of North America · doi:10.1016/s0889-8529(08)70021-5 · Cited by 266
Self-citationTargeting signaling pathways in prostate cancer: mechanisms and clinical trials
He, Y., Xu, W., Xiao, Y., Huang, H., Gu, D., & Ren, S. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-01042-7 · Cited by 287
Costa-Santos, M., Kater, C. E., & Auchus, R. J. (2004) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2003-031021 · Cited by 224
Self-citationAndrogen biosynthesis from cholesterol to DHEA
Miller, W. L. (2002) · Molecular and Cellular Endocrinology · doi:10.1016/s0303-7207(02)00363-5 · Cited by 179
Self-citationRegulation of 17,20 lyase activity by cytochrome b5 and by serine phosphorylation of P450c17
Pandey, A. V., & Miller, W. L. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m414673200 · Cited by 165
Self-citationThe syndrome of 17,20 lyase deficiency
Miller, W. L. (2012) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2011-2161 · Cited by 143
Self-citationGilep, A. A., Sushko, T. A., & Usanov, S. A. (2010) · Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics · doi:10.1016/j.bbapap.2010.06.021 · Cited by 139
Modulation of human CYP19A1 activity by mutant NADPH P450 oxidoreductase
Pandey, A. V., Kempná, P., Hofer, G., Mullis, P. E., & Flück, C. E. (2007) · Molecular Endocrinology · doi:10.1210/me.2007-0245 · Cited by 132
Sherbet, D. P., Tiosano, D., Kwist, K. M., Hochberg, Z., & Auchus, R. J. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m307586200 · Cited by 131
Self-citationBremer, A. A., & Miller, W. L. (2008) · Fertility and Sterility · doi:10.1016/j.fertnstert.2008.02.091 · Cited by 135
Self-citationMashima, Y., Suzuki, Y., Sergeev, Y. V., Ohtake, Y., Tanino, T., Kimura, I., Miyata, H., Aihara, M., Tanihara, H., Inatani, M., et al. (2001) · PubMed · Cited by 131
Androgen synthesis in adrenarche
Miller, W. L. (2009) · Reviews in Endocrine and Metabolic Disorders · doi:10.1007/s11154-008-9102-4 · Cited by 127
Self-citationvan den Akker, E. L. T., Koper, J. W., Boehmer, A. L. M., Themmen, A. P. N., Verhoef-Post, M., Timmerman, M. A., Otten, B. J., Drop, S. L. S., & De Jong, F. H. (2002) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2001-011880 · Cited by 125
Somner, J., McLellan, S., Cheung, J., Mak, Y. T., Frost, M. L., KNAPP, K. M., Wierzbicki, A. S., Wheeler, M. J., Fogelman, I., Ralston, S. H., et al. (2004) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2003-030164 · Cited by 120
Structures of human steroidogenic cytochrome P450 17A1 with substrates
Petrunak, E. M., DeVore, N. M., Porubsky, P. R., & Scott, E. E. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.610998 · Cited by 119
Genetic and clinical features of P450 oxidoreductase deficiency
Scott, R. R., & Miller, W. L. (2008) · Hormone Research in Paediatrics · doi:10.1159/000114857 · Cited by 115
Self-citationThe diverse chemistry of cytochrome P450 17A1 (P450c17, CYP17A1)
Yoshimoto, F. K., & Auchus, R. J. (2014) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2014.11.026 · Cited by 120
Self-citationMartin, R. M., Lin, C. J., Costa, E. M. F., de Oliveira, M. L., Carrilho, A. J. F., Villar, H. C. C. E., Longui, C. A., & Mendonca, B. B. (2003) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2003-030988 · Cited by 106
Cytochrome b5 modulation of 17α hydroxylase and 17–20 lyase (CYP17) activities in steroidogenesis
Akhtar, M. K., Kelly, S. L., & Kaderbhai, M. A. (2005) · Journal of Endocrinology · doi:10.1677/joe.1.06375 · Cited by 104
Gonadal Steroidogenesis in Teleost Fish
Young, G., Kusakabe, M., Nakamura, I., Lokman, P. M., & Goetz, F. W. (2005) · Molecular aspects of fish and marine biology · doi:10.1142/9789812569189_0006 · Cited by 102
Arlt, W., Martens, J. W. M., Song, M., Wang, J. T., Auchus, R. J., & Miller, W. L. (2002) · Endocrinology · doi:10.1210/en.2002-220456 · Cited by 101
Self-citationHershkovitz, E., Parvari, R., Wudy, S. A., Hartmann, M. F., Gomes, L. G., Loewental, N., & Miller, W. L. (2008) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2008-0051 · Cited by 95
Self-citationPolycystic Ovary Syndrome in the Pediatric Population
Bremer, A. A. (2010) · Metabolic Syndrome and Related Disorders · doi:10.1089/met.2010.0039 · Cited by 101
CYP17- and CYP11B-dependent steroid hydroxylases as drug development targets
Hakki, T., & Bernhardt, R. (2006) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2005.07.006 · Cited by 91
The human kidney is a progesterone-metabolizing and androgen-producing organ
Quinkler, M., Bumke-Vogt, C., Meyer, B., Bähr, V., Oelkers, W., & Diederich, S. (2003) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2002-021970 · Cited by 87
Robins, T., Carlsson, J., Sunnerhagen, M., Wedell, A., & Persson, B. (2006) · Molecular Endocrinology · doi:10.1210/me.2006-0172 · Cited by 88
Jagusch, C., Negri, M., Hille, U. E., Hu, Q., Bartels, M., Jahn‐Hoffmann, K., Mendieta, M. A. E. P., Rodenwaldt, B., Müller‐Vieira, U., Schmidt, D., et al. (2007) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2007.10.094 · Cited by 83
Clinical, genetic and enzymatic characterization of P450 oxidoreductase deficiency in four patients
Sahakitrungruang, T., Huang, N., Tee, M. K., Agrawal, V., Russell, W. E., Crock, P., Murphy, N., Migeon, C. J., & Miller, W. L. (2009) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2009-1460 · Cited by 82
Self-citationScott, R. R., Gomes, L. G., Huang, N., Van Vliet, G., & Miller, W. L. (2007) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2006-2345 · Cited by 79
Self-citationKim, Y., Kang, M., Choi, J., Lee, B. H., Kim, G.-H., Ohn, J. H., Kim, S. Y., Park, M. S., & Yoo, H. (2013) · Metabolism · doi:10.1016/j.metabol.2013.08.015 · Cited by 78
Müllerian Inhibiting Substance Inhibits Testosterone Synthesis in Adult Rats
Sriraman, V., Niu, E.-M., Matias, J. R., Donahoe, P. K., MacLaughlin, D. T., HARDY, M. P., & Lee, M. (2001) · Journal of Andrology · doi:10.1002/j.1939-4640.2001.tb02577.x · Cited by 77
Miller, W. L. (2004) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2004.07.005 · Cited by 76
Self-citationTiosano, D., Knopf, C. F., Koren, I., Levanon, N., Hartmann, M. F., Hochberg, Z., & Wudy, S. A. (2008) · European Journal of Endocrinology · doi:10.1530/eje-07-0712 · Cited by 70
Wang, X., Zhang, M. Y. H., Miller, W. L., & Portale, A. A. (2002) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.87.6.8534 · Cited by 71
Self-citationLin, C. J., Martens, J. W. M., & Miller, W. L. (2001) · Molecular Endocrinology · doi:10.1210/mend.15.8.0679 · Cited by 71
Self-citationP450c17 deficiency: clinical and molecular characterization of six patients
Rosa, S., Duff, C., Meyer, M., Lang-Muritano, M., Balercia, G., Boscaro, M., Kemal Topaloglu, A., Mioni, R., Fallo, F., Zuliani, L., et al. (2007) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2006-1486 · Cited by 71
Mechanism of 17α,20-Lyase and New Hydroxylation Reactions of Human Cytochrome P450 17A1
Yoshimoto, F. K., Gonzalez, E. R., Auchus, R. J., & Guengerich, F. P. (2016) · Journal of Biological Chemistry · doi:10.1074/jbc.m116.732966 · Cited by 72
Self-citationThe next 150 years of congenital adrenal hyperplasia
Turcu, A. F., & Auchus, R. J. (2015) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2015.05.013 · Cited by 69
Self-citationTee, M. K., & Miller, W. L. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.460048 · Cited by 72
Self-citationMendieta, M. A. E. P., Negri, M., Jagusch, C., Müller‐Vieira, U., Lauterbach, T., & Hartmann, R. W. (2008) · Journal of Medicinal Chemistry · doi:10.1021/jm800355c · Cited by 69
Hlavica, P., Schulze, J., & Lewis, D. F. V. (2003) · Journal of Inorganic Biochemistry · doi:10.1016/s0162-0134(03)00152-1 · Cited by 69
Lam, C.-W., Arlt, W., Chan, C.-K., Honour, J. W., Lin, C. J., Tong, S.-F., Choy, K.-W., & Miller, W. L. (2001) · Molecular Genetics and Metabolism · doi:10.1006/mgme.2000.3134 · Cited by 65
Self-citationActive site proton delivery and the lyase activity of human CYP17A1
Khatri, Y., Gregory, M. C., Grinkova, Y. V., Denisov, I. G., & Sligar, S. G. (2013) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2013.11.094 · Cited by 64
Yang, J., Cui, B., Sun, S., Shi, T., Zheng, S., Bi, Y., Liu, J., Zhao, Y., Chen, J., Ning, G., et al. (2006) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2005-2283 · Cited by 63
Deletion of the Mouse P450c17 Gene Causes Early Embryonic Lethality
Bair, S. R., & Mellon, S. H. (2004) · Molecular and Cellular Biology · doi:10.1128/mcb.24.12.5383-5390.2004 · Cited by 63
Inhibition of CYP 17, a New Strategy for the Treatment of Prostate Cancer
Hartmann, R. W., Ehmer, P. B., Haidar, S., Hector, M., Jose, J., Klein, C. D. P., Seidel, S. B., Sergejew, T. F., Wachall, B. G., Wächter, G. A., et al. (2002) · Archiv der Pharmazie · doi:10.1002/1521-4184(200204)335:4 · Cited by 61
The molecular basis of premature adrenarche: an hypothesis
Miller, W. L. (1999) · Acta Paediatrica · doi:10.1111/j.1651-2227.1999.tb14405.x · Cited by 60
Self-citationHu, Q., Negri, M., Jahn‐Hoffmann, K., Zhuang, Y., Ölgen, S., Bartels, M., Müller‐Vieira, U., Lauterbach, T., & Hartmann, R. W. (2008) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2008.07.011 · Cited by 60
Krone, N. P., Riepe, F. G., Götze, D., Korsch, E., Rister, M., Commentz, J., Partsch, C., Grötzinger, J., Peter, M., & Sippell, W. G. (2005) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2005-0089 · Cited by 58
Marohnic, C. C., Panda, S. P., Martásek, P., & Masters, B. S. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m607095200 · Cited by 57
P450 oxidoreductase deficiency: a new form of congenital adrenal hyperplasia
Flück, C. E., & Miller, W. L. (2006) · Current Opinion in Pediatrics · doi:10.1097/01.mop.0000236395.71956.5c · Cited by 57
Self-citationPitfalls in characterizing P450c17 mutations associated with isolated 17,20 lyase deficiency
Gupta, M. K., Geller, D. H., & Auchus, R. J. (2001) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.86.9.7812 · Cited by 59
Self-citationLocke, J. A., Nelson, C. C., Adomat, H. H., Hendy, S. C., Gleave, M. E., & Guns, E. S. T. (2009) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2009.03.011 · Cited by 58
Tee, M. K., Dong, Q., & Miller, W. L. (2008) · Endocrinology · doi:10.1210/en.2007-1527 · Cited by 55
Self-citationOrganization of Cytochrome P450 Enzymes Involved in Sex Steroid Synthesis
Praporski, S., Ng, S. M., Nguyen, A. D., Corbin, C. J., Mechler, Á., Zheng, J., Conley, A. J., & Martin, L. L. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.006064 · Cited by 55
Biason‐Lauber, A., Kempken, B., WERDER, E. A., Forest, M. G., Einaudi, S., Ranke, M. B., Matsuo, N., Brunelli, V., Schönle, E., & ZACHMANN, M. (2000) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.85.3.6475 · Cited by 58
Genetic variation in human P450 oxidoreductase
Miller, W. L., Huang, N., Agrawal, V., & Giacomini, K. M. (2009) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2008.09.017 · Cited by 54
Self-citationBhatt, M. R., Khatri, Y., Rodgers, R. J., & Martin, L. L. (2016) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2016.02.033 · Cited by 54
Disorders of Androgen Synthesis – from Cholesterol to Dehydroepiandrosterone
Miller, W. L. (2005) · Medical Principles and Practice · doi:10.1159/000086185 · Cited by 53
Self-citationThe post-translational regulation of 17,20 lyase activity
Miller, W. L., & Tee, M. K. (2014) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2014.09.010 · Cited by 52
Self-citationThe Adrenal Cortex and its Disorders
Miller, W. L. (2009) · Wiley eBooks · doi:10.1002/9781444316728.ch13 · Cited by 51
Self-citationHormonal Therapies for Individuals with Intersex Conditions
Warne, G. L., Grover, S. R., & Zajac, J. D. (2005) · Treatments in Endocrinology · doi:10.2165/00024677-200504010-00003 · Cited by 48
Dhir, V., Reisch, N., Bleicken, C., Lebl, J., Kamrath, C., Schwarz, H., Grötzinger, J., Sippell, W. G., Riepe, F. G., Arlt, W., et al. (2009) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2009-0172 · Cited by 46
Wei, J., Wei, J., Li, W., Yun-sheng, B., & Wei, F. (2006) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2006-0153 · Cited by 45
Lepesheva, G. I., Podust, L. M., Bellamine, A., & Waterman, M. R. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m102767200 · Cited by 45
Swart, A. C., Storbeck, K., & Swart, P. (2010) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2009.12.014 · Cited by 44
Adrenal cortex and its disorders
Miller, W. L., & Flück, C. E. (2014) · Elsevier eBooks · doi:10.1016/b978-1-4557-4858-7.00022-6 · Cited by 45
Self-citationHuang, N., Dardis, A., & Miller, W. L. (2005) · Molecular Endocrinology · doi:10.1210/me.2004-0411 · Cited by 42
Self-citationSamtani, R., Bajpai, M., Vashisht, K., Ghosh, P., & Saraswathy, K. N. (2011) · The Journal of Urology · doi:10.1016/j.juro.2011.02.043 · Cited by 42
Auchus, R. J., Sampath Kumar, A., Andrew Boswell, C., Gupta, M. K., Bruce, K., Rath, N. P., & Covey, D. F. (2003) · Archives of Biochemistry and Biophysics · doi:10.1016/s0003-9861(02)00491-5 · Cited by 39
Self-citationCatalytically Relevant Electrostatic Interactions of Cytochrome P450c17 (CYP17A1) and Cytochrome b5
Peng, H., Liu, J., Forsberg, S. E., Tran, H. T., Anderson, S. M., & Auchus, R. J. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.608919 · Cited by 39
Self-citationP450 Enzymes in Steroid Processing
Auchus, R. J., & Miller, W. L. (2015) · Springer eBooks · doi:10.1007/978-3-319-12108-6_12 · Cited by 41
Self-citationPandey, A. V., Flück, C. E., Huang, N., Tajima, T., Fujieda, K., & Miller, W. L. (2004) · Endocrine Research · doi:10.1081/erc-200044134 · Cited by 38
Self-citationYoshimoto, F. K., Zhou, Y., Peng, H.-M., Stidd, D., Yoshimoto, J. A., Sharma, K. K., Matthew, S., & Auchus, R. J. (2012) · Biochemistry · doi:10.1021/bi300895w · Cited by 38
Self-citationSreenivasulu, G., & Senthilkumaran, B. (2009) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2009.03.004 · Cited by 38
Patócs, A., Likó, I., Varga, I., Gergics, P., Boros, A. M., Fütő, L., Kun, I. Z., Bertalan, R. Á., Tóth, S., Pázmány, T., et al. (2005) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2005.06.035 · Cited by 36
Qiao, J. (2003) · Molecular and Cellular Endocrinology · doi:10.1016/s0303-7207(02)00156-9 · Cited by 36
Mechanism of Cytochrome P450 17A1-Catalyzed Hydroxylase and Lyase Reactions
Bonomo, S., Jørgensen, F. S., & Olsen, L. (2017) · Journal of Chemical Information and Modeling · doi:10.1021/acs.jcim.6b00759 · Cited by 35
Novel Steroidal Vinyl Fluorides as Inhibitors of Steroid C17(20) Lyase
Burkhart, J. P., Weintraub, P. M., Gates, C. A., Resvick, R. J., Vaz, R. J., Friedrich, D., Angelastro, M. R., Bey, P., & Peet, N. P. (2002) · Bioorganic & Medicinal Chemistry · doi:10.1016/s0968-0896(01)00354-6 · Cited by 33
Janner, M., Pandey, A. V., Mullis, P. E., & Flück, C. E. (2006) · European Journal of Endocrinology · doi:10.1530/eje.1.02172 · Cited by 33
Direct electrochemistry of human, bovine and porcine cytochrome P450c17
Johnson, D. L., Conley, A. J., & Martin, L. L. (2005) · Journal of Molecular Endocrinology · doi:10.1677/jme.1.01971 · Cited by 32
Takeda, Y., Yoneda, T., Demura, M., Furukawa, K., KOSHIDA, H., Miyamori, I., & Mabuchi, H. (2001) · Clinical Endocrinology · doi:10.1046/j.1365-2265.2001.01272.x · Cited by 31
Wang, Y., Tee, M. K., & Miller, W. L. (2010) · Endocrinology · doi:10.1210/en.2009-1247 · Cited by 31
Self-citationCytochromes P450—A Family of Proteins and Scientists–Understanding their Relationships
Masters, B. S. S., & Marohnic, C. C. (2006) · Drug Metabolism Reviews · doi:10.1080/03602530600570065 · Cited by 31
Molecular modeling of mammalian cytochrome P450s
Dai, R., Pincus, M. R., & Friedman, F. K. (2000) · Cellular and Molecular Life Sciences · doi:10.1007/pl00000709 · Cited by 32
Qiao, J., Chen, X., Zuo, C., Gu, Y., Liu, B., Liang, J., Lu, Y., Tang, J., Wu, Y., Chen, M., et al. (2010) · Clinical Endocrinology · doi:10.1111/j.1365-2265.2009.03607.x · Cited by 30
Pattison, J. C., Abbott, D. H., Wendy Saltzman, A., Conley, A. J., & Bird, I. M. (2009) · Journal of Endocrinology · doi:10.1677/joe-08-0554 · Cited by 31
Müssig, K., Kaltenbach, S., Machicao, F. E., Maser‐Gluth, C., Hartmann, M. F., Wudy, S. A., Schnauder, G., Häring, H., Seif, F. J., & Gallwitz, B. (2005) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2005-0136 · Cited by 30
Mendieta, M. A. E. P., Negri, M., Jagusch, C., Hille, U. E., Müller‐Vieira, U., Schmidt, D., Hansen, K., & Hartmann, R. W. (2007) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2007.10.079 · Cited by 29
Miller, W. L. (2012) · Science Signaling · doi:10.1126/scisignal.2003318 · Cited by 31
Self-citationWhy human cytochrome P450c21 is a progesterone 21-hydroxylase
Mizrachi, D., Wang, Z., Sharma, K. K., Gupta, M. K., Xu, K., Dwyer, C. R., & Auchus, R. J. (2011) · Biochemistry · doi:10.1021/bi102078e · Cited by 28
Self-citationPechurskaya, T. A., Lukashevich, O. P., Gilep, A. A., & Usanov, S. A. (2008) · Biochemistry (Moscow) · doi:10.1134/s0006297908070092 · Cited by 28
Metadata
- Authors
- Auchus, R. J., & Miller, W. L.
- Affiliations
- University of California, San Francisco (US)
- Corresponding author
- Miller, Walter L.
- Venue
- Molecular Endocrinology
- Publisher
- The Endocrine Society
- Published
- 1999-07
- Volume
- 13
- Issue
- 7
- Pages
- 1169-1182
- ISSN
- 0888-8809 (ISSN-L)
- 1944-9917
- OpenAlex
- W2112100343
- Cited by
- 185
- References
- 71
- Citations by year
- 2025: 3 · 2024: 1 · 2022: 2 · 2021: 4 · 2020: 1 · 2019: 1 · 2018: 1 · 2017: 2 · 2016: 5 · 2015: 7 · 2014: 8 · 2013: 8 · 2012: 8
- FWCI
- 6.63
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Molecular Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (P41 RP-01081, 5r01dk042154-09)
- University of California, San Francisco
- National Institute of Diabetes and Digestive and Kidney Diseases (DK-37922, DK 42154, R01DK037922)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (U54-HD34449, U54HD034449)
- Topics
- Physical Sciences › Chemistry › Inorganic Chemistry › Metal-Catalyzed Oxygenation Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Physical Sciences › Chemistry › Organic Chemistry › Steroid Chemistry and Biochemistry
- Keywords
- CYP17, 17α-hydroxylase/17,20-lyase, steroid hydroxylation, steroidogenesis, androgen production, estrogen synthesis, active site structure, substrate specificity, regioselectivity, hydrogen abstraction, pregnenolone, progesterone, molecular docking, molecular dynamics simulation
- MeSH terms
- Amino Acid Sequence, Bacterial Proteins, Binding Sites, Cytochrome P-450 Enzyme System, Heme, Humans, Mixed Function Oxygenases, Models, Molecular, Molecular Sequence Data, Mutation, NADPH-Ferrihemoprotein Reductase, Pregnenolone, Protein Conformation, Steroid 17-alpha-Hydroxylase, Mutagenesis, Site-Directed, Sequence Homology, Amino Acid
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
