4P6S

Crystal Structure of tyrosinase from Bacillus megaterium with L-DOPA in the active site

Summary for 4P6S

• Entry DOI: 10.2210/pdb4p6s/pdb
• Related: 4P6R 4P6T
• Descriptor: Tyrosinase, ZINC ION, 3,4-DIHYDROXYPHENYLALANINE, ... (4 entities in total)
• Functional Keywords: l-dopa, type 3 copper proteins, oxidoreductase
• Biological source: Bacillus megaterium
• Total number of polymer chains: 2
• Total formula weight: 67759.74

Authors

Goldfeder, M.,Kanteev, M.,Adir, N.,Fishman, A. (deposition date: 2014-03-25, release date: 2014-07-30, Last modification date: 2023-12-27)

Primary citation

Goldfeder, M.,Kanteev, M.,Isaschar-Ovdat, S.,Adir, N.,Fishman, A.
Determination of tyrosinase substrate-binding modes reveals mechanistic differences between type-3 copper proteins.
Nat Commun, 5:4505-4505, 2014

PubMed Abstract: Tyrosinase is responsible for the two initial enzymatic steps in the conversion of tyrosine to melanin. Many tyrosinase mutations are the leading cause of albinism in humans, and it is a prominent biotechnology and pharmaceutical industry target. Here we present crystal structures that show that both monophenol hydroxylation and diphenol oxidation occur at the same site. It is suggested that concurrent presence of a phenylalanine above the active site and a restricting thioether bond on the histidine coordinating CuA prevent hydroxylation of monophenols by catechol oxidases. Furthermore, a conserved water molecule activated by E195 and N205 is proposed to mediate deprotonation of the monophenol at the active site. Overall, the structures reveal precise steps in the enzymatic catalytic cycle as well as differences between tyrosinases and other type-3 copper enzymes.

PubMed: 25074014
DOI: 10.1038/ncomms5505

Experimental method

X-RAY DIFFRACTION (2.2 Å)