The Crystal Structure of Tyrosinase from Verrucomicrobium spinosum Reveals It to Be an Atypical Bacterial Tyrosinase
(2023) In Biomolecules 13(9).- Abstract
Tyrosinases belong to the type-III copper enzyme family, which is involved in melanin production in a wide range of organisms. Despite similar overall characteristics and functions, their structures, activities, substrate specificities and regulation vary. The tyrosinase from the bacterium Verrucomicrobium spinosum (vsTyr) is produced as a pre-pro-enzyme in which a C-terminal extension serves as an inactivation domain. It does not require a caddie protein for copper ion incorporation, which makes it similar to eukaryotic tyrosinases. To gain an understanding of the catalytic machinery and regulation of vsTyr activity, we determined the structure of the catalytically active “core domain” of vsTyr by X-ray crystallography. The analysis... (More)
Tyrosinases belong to the type-III copper enzyme family, which is involved in melanin production in a wide range of organisms. Despite similar overall characteristics and functions, their structures, activities, substrate specificities and regulation vary. The tyrosinase from the bacterium Verrucomicrobium spinosum (vsTyr) is produced as a pre-pro-enzyme in which a C-terminal extension serves as an inactivation domain. It does not require a caddie protein for copper ion incorporation, which makes it similar to eukaryotic tyrosinases. To gain an understanding of the catalytic machinery and regulation of vsTyr activity, we determined the structure of the catalytically active “core domain” of vsTyr by X-ray crystallography. The analysis showed that vsTyr is an atypical bacterial tyrosinase not only because it is independent of a caddie protein but also because it shows the highest structural (and sequence) similarity to plant-derived members of the type-III copper enzyme family and is more closely related to fungal tyrosinases regarding active site features. By modelling the structure of the pre-pro-enzyme using AlphaFold, we observed that Phe453, located in the C-terminal extension, is appropriately positioned to function as a “gatekeeper” residue. Our findings raise questions concerning the evolutionary origin of vsTyr.
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- author
- Fekry, Mostafa ; Dave, Khyati K. ; Badgujar, Dilip ; Hamnevik, Emil ; Aurelius, Oskar LU ; Dobritzsch, Doreen and Danielson, U. Helena
- organization
- publishing date
- 2023-09
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- crystal structure, tyrosinase, Verrucomicrobium spinosum
- in
- Biomolecules
- volume
- 13
- issue
- 9
- article number
- 1360
- publisher
- MDPI AG
- external identifiers
-
- pmid:37759761
- scopus:85172456580
- ISSN
- 2218-273X
- DOI
- 10.3390/biom13091360
- language
- English
- LU publication?
- yes
- id
- 96805c36-52cb-4014-aad6-9e210ef68dd2
- date added to LUP
- 2023-12-11 14:12:38
- date last changed
- 2024-04-24 07:41:37
@article{96805c36-52cb-4014-aad6-9e210ef68dd2,
abstract = {{<p>Tyrosinases belong to the type-III copper enzyme family, which is involved in melanin production in a wide range of organisms. Despite similar overall characteristics and functions, their structures, activities, substrate specificities and regulation vary. The tyrosinase from the bacterium Verrucomicrobium spinosum (vsTyr) is produced as a pre-pro-enzyme in which a C-terminal extension serves as an inactivation domain. It does not require a caddie protein for copper ion incorporation, which makes it similar to eukaryotic tyrosinases. To gain an understanding of the catalytic machinery and regulation of vsTyr activity, we determined the structure of the catalytically active “core domain” of vsTyr by X-ray crystallography. The analysis showed that vsTyr is an atypical bacterial tyrosinase not only because it is independent of a caddie protein but also because it shows the highest structural (and sequence) similarity to plant-derived members of the type-III copper enzyme family and is more closely related to fungal tyrosinases regarding active site features. By modelling the structure of the pre-pro-enzyme using AlphaFold, we observed that Phe453, located in the C-terminal extension, is appropriately positioned to function as a “gatekeeper” residue. Our findings raise questions concerning the evolutionary origin of vsTyr.</p>}},
author = {{Fekry, Mostafa and Dave, Khyati K. and Badgujar, Dilip and Hamnevik, Emil and Aurelius, Oskar and Dobritzsch, Doreen and Danielson, U. Helena}},
issn = {{2218-273X}},
keywords = {{crystal structure; tyrosinase; Verrucomicrobium spinosum}},
language = {{eng}},
number = {{9}},
publisher = {{MDPI AG}},
series = {{Biomolecules}},
title = {{The Crystal Structure of Tyrosinase from Verrucomicrobium spinosum Reveals It to Be an Atypical Bacterial Tyrosinase}},
url = {{http://dx.doi.org/10.3390/biom13091360}},
doi = {{10.3390/biom13091360}},
volume = {{13}},
year = {{2023}},
}