Please use this identifier to cite or link to this item: http://repositorio.unicamp.br/jspui/handle/REPOSIP/328201
Type: Artigo
Title: Functional And Structural Consequences Of Nine Cyp21a2 Mutations Ranging From Very Mild To Severe Effects
Author: Michelatto
Debora de Paula; Karlsson
Leif; Gori Lusa
Ana Leticia; Mgnani Silva
Camila D'Almeida; Ostberg
Linus Joakim; Persson
Bengt; Guerra-Junior
Gil; Valente de Lemos-Marini
Sofia Helena; Barbaro
Michela; de Mello
Maricilda Palandi; Lajic
Svetlana
Abstract: We present the functional and structural effects of seven novel (p.Leu12Met, p.Arg16Cys, p.Ser101Asn, p.Ser202Gly, p.Pro267Leu, p.Gln389 Ala391del, and p.Thr450Met) and two previously reported but not studied (p.Ser113Phe and p.Thr450Pro) CYP21A2 mutations. Functional analyses were complemented with in silico prediction of mutation pathogenicity based on the recently crystallized human CYP21A2 structure. Mutated proteins were transiently expressed in COS-1 cells and enzyme activities towards 17-hydroxyprogesterone and progesterone were determined. Residual enzyme activities between 43% and 97% were obtained for p.Arg16Cys, p.Ser101Asn, p.Ser202Gly, p.Pro267Leu, and p.Thr450Met, similar to the activities of the well-known nonclassic mutations p.Pro453Ser and p.Pro482Ser, whereas the p.Leu12Met variant showed an activity of 100%. Conversely, the novel p.Ser113Phe, p. Gln389 Ala391del, and p.Thr450Promutations drastically reduced the enzyme function below 4%. The K-m values for all novel variants were in the same order of magnitude as for the wild-type protein except for p.The450Met. The maximum velocity was decreased for all mutants except for p.Leu12Met. We conclude that p. Leu12Met is a normal variant; the mutations p.Arg16Cys, p.Ser101Asn, p.Ser202Gly, p.Pro267Leu, and p.Thr450Met could be associated with very mild nonclassic CAH, and the mutations p.Ser113Phe, p.Gln389 Ala391del, and p.Thr450Pro are associated with classic CAH. The obtained residual activities indicated a good genotype-phenotype correlation.
Editor: Hindawi Publishing Corp
New York
Citation: International Journal Of Endocrinology. Hindawi Publishing Corp, p. , 2016.
Rights: aberto
Identifier DOI: 10.1155/2016/4209670
Address: https://www.hindawi.com/journals/ije/2016/4209670/
Date Issue: 2016
Appears in Collections:Unicamp - Artigos e Outros Documentos

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