PMID- 10198222
OWN - NLM
STAT- MEDLINE
DCOM- 19990524
LR  - 20161124
IS  - 0006-291X (Print)
IS  - 0006-291X (Linking)
VI  - 257
IP  - 2
DP  - 1999 Apr 13
TI  - Effects of missense mutations and deletions on membrane anchoring and enzyme
      function of human steroid 21-hydroxylase (P450c21).
PG  - 384-90
AB  - We studied membrane binding and enzyme function of six variant forms of human
      steroid 21-hydroxylase (P450c21), a mutant (P30Q) from a patient with congenital 
      adrenal hyperplasia, four artificial deletions in the amino terminal region
      (delS1 and del S2; the first and second hydrophobic segment, delS3; the region in
      between, delS4; the combination of these), and one naturally ocurring
      polymorphism in a region implicated to be critical for membrane integration
      (delL10). Enzyme function was assayed after transient expression in COS-1 cells, 
      and membrane binding was studied by coupled in vitro transcription-translation in
      the presence of microsomal membranes. P450c21(delS1) retained some enzyme
      activity but showed severely reduced membrane binding. P450c21(P30Q), P450c21
      (delS2), P450c21(delS3), and P450c21(delS4) had abolished enzyme function.
      P450c21(P30Q) and P450c21 (delS2) did not affect membrane binding, P450c21
      (delS3) had slightly reduced binding with a qualitative difference suggested by
      the absence of a glycosylated form of the protein, and P450c21(delS4) had
      abolished membrane integration. No significant differences could be identified
      for the delL10 variant. These data support that P450c21 spans the membrane
      through its first hydrophobic domain only, and that the protein lacking this
      segment retains sufficiently normal structure to enable catalysis. They also
      confirm that P30Q is responsible for the severe phenotype of the patient in which
      it was found, and indicate that the common delL10 polymorphism does not have a
      major effect on enzyme function.
CI  - Copyright 1999 Academic Press.
FAU - Lajic, S
AU  - Lajic S
AD  - Department of Molecular Medicine, Karolinska Hospital, Stockholm, 171 76, Sweden.
      Svetlana.Lajic@cmm.di.se
FAU - Nikoshkov, A
AU  - Nikoshkov A
FAU - Holst, M
AU  - Holst M
FAU - Wedell, A
AU  - Wedell A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 4G7DS2Q64Y (Progesterone)
RN  - 68-96-2 (17-alpha-Hydroxyprogesterone)
RN  - EC 1.14.14.16 (Steroid 21-Hydroxylase)
SB  - IM
MH  - 17-alpha-Hydroxyprogesterone/metabolism
MH  - Adrenal Hyperplasia, Congenital/enzymology/genetics
MH  - Amino Acid Sequence
MH  - Animals
MH  - COS Cells
MH  - Cell Fractionation
MH  - Cell Membrane/enzymology/*metabolism
MH  - Cytosol/enzymology/metabolism
MH  - DNA Mutational Analysis
MH  - Female
MH  - *Gene Deletion
MH  - Glycosylation
MH  - Heterozygote
MH  - Humans
MH  - Kinetics
MH  - Microsomes/enzymology/metabolism
MH  - Molecular Sequence Data
MH  - Mutation, Missense/*genetics
MH  - Polymorphism, Genetic
MH  - Progesterone/metabolism
MH  - Steroid 21-Hydroxylase/genetics/*metabolism
MH  - Transfection
EDAT- 1999/04/13 00:00
MHDA- 1999/04/13 00:01
CRDT- 1999/04/13 00:00
PHST- 1999/04/13 00:00 [pubmed]
PHST- 1999/04/13 00:01 [medline]
PHST- 1999/04/13 00:00 [entrez]
AID - S0006-291X(99)90482-5 [pii]
AID - 10.1006/bbrc.1999.0482 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 1999 Apr 13;257(2):384-90. doi:
      10.1006/bbrc.1999.0482.