Heme a synthase in bacteria depends on one pair of cysteinyls for activity.
(2016) In Biochimica et Biophysica Acta 1857(2). p.160-168- Abstract
- Heme A is a prosthetic group unique for cytochrome a-type respiratory oxidases in mammals, plants and many microorganisms. The poorly understood integral membrane protein heme A synthase catalyzes the synthesis of heme A from heme O. In bacteria, but not in mitochondria, this enzyme contains one or two pairs of cysteine residues that are present in predicted hydrophilic polypeptide loops on the extracytoplasmic side of the membrane. We used heme A synthase from the eubacterium Bacillus subtilis and the hyperthermophilic archeon Aeropyrum pernix to investigate the functional role of these cysteine residues. Results with B. subtilis amino acid substituted proteins indicated the pair of cysteine residues in the loop connecting transmembrane... (More)
- Heme A is a prosthetic group unique for cytochrome a-type respiratory oxidases in mammals, plants and many microorganisms. The poorly understood integral membrane protein heme A synthase catalyzes the synthesis of heme A from heme O. In bacteria, but not in mitochondria, this enzyme contains one or two pairs of cysteine residues that are present in predicted hydrophilic polypeptide loops on the extracytoplasmic side of the membrane. We used heme A synthase from the eubacterium Bacillus subtilis and the hyperthermophilic archeon Aeropyrum pernix to investigate the functional role of these cysteine residues. Results with B. subtilis amino acid substituted proteins indicated the pair of cysteine residues in the loop connecting transmembrane segments I and II as being essential for catalysis but not required for binding of the enzyme substrate, heme O. Experiments with isolated A. pernix and B. subtilis heme A synthase demonstrated that a disulfide bond can form between the cysteine residues in the same loop and also between loops showing close proximity of the two loops in the folded enzyme protein. Based on the findings we propose a classification scheme for the four discrete types of heme A synthase found so far in different organisms and propose that essential cysteinyls mediate transfer of reducing equivalents required for the oxygen-dependent catalysis of heme A synthesis from heme O. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/8234915
- author
- Lewin, Anna LU and Hederstedt, Lars LU
- organization
- publishing date
- 2016
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Heme biosynthesis, Cytochrome a, Bacillus subtilis, Aeropyrum pernix, CtaA, COX15, Protein disulfide
- in
- Biochimica et Biophysica Acta
- volume
- 1857
- issue
- 2
- pages
- 160 - 168
- publisher
- Elsevier
- external identifiers
-
- pmid:26592143
- wos:000368204400004
- scopus:84950000434
- pmid:26592143
- ISSN
- 0006-3002
- DOI
- 10.1016/j.bbabio.2015.11.008
- language
- English
- LU publication?
- yes
- id
- 8241b1fb-0286-4f82-b588-8fc56c60703a (old id 8234915)
- date added to LUP
- 2016-04-01 12:56:42
- date last changed
- 2025-04-04 14:53:10
@article{8241b1fb-0286-4f82-b588-8fc56c60703a,
abstract = {{Heme A is a prosthetic group unique for cytochrome a-type respiratory oxidases in mammals, plants and many microorganisms. The poorly understood integral membrane protein heme A synthase catalyzes the synthesis of heme A from heme O. In bacteria, but not in mitochondria, this enzyme contains one or two pairs of cysteine residues that are present in predicted hydrophilic polypeptide loops on the extracytoplasmic side of the membrane. We used heme A synthase from the eubacterium Bacillus subtilis and the hyperthermophilic archeon Aeropyrum pernix to investigate the functional role of these cysteine residues. Results with B. subtilis amino acid substituted proteins indicated the pair of cysteine residues in the loop connecting transmembrane segments I and II as being essential for catalysis but not required for binding of the enzyme substrate, heme O. Experiments with isolated A. pernix and B. subtilis heme A synthase demonstrated that a disulfide bond can form between the cysteine residues in the same loop and also between loops showing close proximity of the two loops in the folded enzyme protein. Based on the findings we propose a classification scheme for the four discrete types of heme A synthase found so far in different organisms and propose that essential cysteinyls mediate transfer of reducing equivalents required for the oxygen-dependent catalysis of heme A synthesis from heme O.}},
author = {{Lewin, Anna and Hederstedt, Lars}},
issn = {{0006-3002}},
keywords = {{Heme biosynthesis; Cytochrome a; Bacillus subtilis; Aeropyrum pernix; CtaA; COX15; Protein disulfide}},
language = {{eng}},
number = {{2}},
pages = {{160--168}},
publisher = {{Elsevier}},
series = {{Biochimica et Biophysica Acta}},
title = {{Heme a synthase in bacteria depends on one pair of cysteinyls for activity.}},
url = {{http://dx.doi.org/10.1016/j.bbabio.2015.11.008}},
doi = {{10.1016/j.bbabio.2015.11.008}},
volume = {{1857}},
year = {{2016}},
}