PDBsum entry 4p6r

Oxidoreductase

PDB id: 4p6r

Contents

Protein chains

287 a.a.

Ligands

TYR ×2

Metals

_ZN ×4

Waters ×224

PDB id:

4p6r

Name:

Oxidoreductase

Title:

Crystal structure of tyrosinase from bacillus megaterium with tyrosine in the active site

Structure:

Tyrosinase. Chain: a, b. Fragment: unp residues 4-290. Engineered: yes

Source:

Bacillus megaterium. Organism_taxid: 1404. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.

Resolution:

2.20Å R-factor: 0.194 R-free: 0.241

Authors:

M.Goldfeder,M.Kanteev,N.Adir,A.Fishman

Key ref:

M.Goldfeder et al. (2014). Determination of tyrosinase substrate-binding modes reveals mechanistic differences between type-3 copper proteins. Nat Commun, 5, 4505. PubMed id: 25074014 DOI: 10.1038/ncomms5505

Date:

25-Mar-14 Release date: 30-Jul-14

Protein chains

B2ZB02  (B2ZB02_PRIMG) -  Tyrosinase from Priestia megaterium

Seq: 297 a.a.

Struc: 287 a.a.

Enzyme reactions

• Enzyme class: E.C.1.14.18.1 - tyrosinase.
• Pathway: Melanin Biosynthesis
• Reaction:
  1. L-tyrosine + O2 = L-dopaquinone + H2O
  2. 2 L-dopa + O2 = 2 L-dopaquinone + 2 H2O

L-tyrosine (Bound ligand (Het Group name = TYR) corresponds exactly) + O2 = L-dopaquinone + H2O

2 × L-dopa (Bound ligand (Het Group name = TYR) matches with 92.86% similarity) + O2 = 2 × L-dopaquinone + 2 × H2O

• Cofactor: Cu cation

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

DOI no: 10.1038/ncomms5505

Nat Commun 5:4505 (2014)

PubMed id: 25074014

Determination of tyrosinase substrate-binding modes reveals mechanistic differences between type-3 copper proteins.

M.Goldfeder, M.Kanteev, S.Isaschar-Ovdat, N.Adir, A.Fishman.

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.