PDBsum entry 3hhs

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protein metals Protein-protein interface(s) links
Oxidoreductase PDB id
Protein chains
669 a.a. *
656 a.a. *
_CU ×4
Waters ×1195
* Residue conservation analysis
PDB id:
Name: Oxidoreductase
Title: Crystal structure of manduca sexta prophenoloxidase
Structure: Phenoloxidase subunit 2. Chain: a. Synonym: propo-p2. Phenoloxidase subunit 1. Chain: b. Synonym: propo-p1. Ec:
Source: Manduca sexta. Carolina sphinx,hornblower,tobacco hawkmot hornworm. Organism_taxid: 7130. Other_details: tissue. Other_details: tissue
1.97Å     R-factor:   0.156     R-free:   0.194
Authors: Y.Li,Y.Wang,H.Jiang,J.Deng
Key ref:
Y.Li et al. (2009). Crystal structure of Manduca sexta prophenoloxidase provides insights into the mechanism of type 3 copper enzymes. Proc Natl Acad Sci U S A, 106, 17002-17006. PubMed id: 19805072 DOI: 10.1073/pnas.0906095106
17-May-09     Release date:   29-Sep-09    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
Q25519  (PRP2_MANSE) -  Phenoloxidase subunit 2
695 a.a.
669 a.a.
Protein chain
Pfam   ArchSchema ?
O44249  (PRP1_MANSE) -  Phenoloxidase subunit 1
685 a.a.
656 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: Chains A, B: E.C.  - Tyrosinase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

Melanin Biosynthesis
1. 2 L-dopa + O2 = 2 dopaquinone + 2 H2O
2. L-tyrosine + O2 = dopaquinone + H2O
2 × L-dopa
+ O(2)
= 2 × dopaquinone
+ 2 × H(2)O
+ O(2)
= dopaquinone
+ H(2)O
      Cofactor: Cu cation
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     extracellular region   1 term 
  Biological process     metabolic process   6 terms 
  Biochemical function     oxidoreductase activity     6 terms  


DOI no: 10.1073/pnas.0906095106 Proc Natl Acad Sci U S A 106:17002-17006 (2009)
PubMed id: 19805072  
Crystal structure of Manduca sexta prophenoloxidase provides insights into the mechanism of type 3 copper enzymes.
Y.Li, Y.Wang, H.Jiang, J.Deng.
Arthropod phenoloxidase (PO) generates quinones and other toxic compounds to sequester and kill pathogens during innate immune responses. It is also involved in wound healing and other physiological processes. Insect PO is activated from its inactive precursor, prophenoloxidase (PPO), by specific proteolysis via a serine protease cascade. Here, we report the crystal structure of PPO from a lepidopteran insect at a resolution of 1.97 A, which is the initial structure for a PPO from the type 3 copper protein family. Manduca sexta PPO is a heterodimer consisting of 2 homologous polypeptide chains, PPO1 and PPO2. The active site of each subunit contains a canonical type 3 di-nuclear copper center, with each copper ion coordinated with 3 structurally conserved histidines. The acidic residue Glu-395 located at the active site of PPO2 may serve as a general base for deprotonation of monophenolic substrates, which is key to the ortho-hydroxylase activity of PO. The structure provides unique insights into the mechanism by which type 3 copper proteins differ in their enzymatic activities, albeit sharing a common active center. A drastic change in electrostatic surface induced on cleavage at Arg-51 allows us to propose a model for localized PPO activation in insects.
  Selected figure(s)  
Figure 1.
Overall structure of M. sexta PPO. (A) The heterodimeric PPO is formed in a back-to-back mode. PPO1 and PPO2 are shown in green and yellow, respectively. (B) Domains of PPO2 are colored as follows: pro-region, purple; domain I, blue; domain II, yellow; domain III, green. The di-copper atoms are located in domain II and are shown as red spheres. The proteolytic site R51 residue is shown in the stick. The amino-terminus and carboxyl-terminus of PPO2 are indicated as N and C, respectively.
Figure 2.
Di-copper center in M. sexta PPO2. The active site of PPO2 can be superimposed well with that of oxygenated Limulus polyphemus hemocyanin (Lp-HC, PDB ID code 1OXY). The secondary structures of PPO2 are shown in the ribbon and colored in yellow. The 6 copper-coordinating His ligands are shown as sticks, with those from Lp-HC colored green. The di-copper atoms are shown as spheres: PPO2, red; Lp-HC, purple. The peroxide ion in Lp-HC is shown as brown spheres. Notice the unique E395 in PPO2, which is located near the substrate place holder F88. E395 could be a base for phenol deprotonation, which is key to the ortho-phenol hydroxylation activity of PPO.
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21181151 Y.Kawamura-Konishi, S.Maekawa, M.Tsuji, and H.Goto (2011).
C-terminal processing of tyrosinase is responsible for activation of Pholiota microspora proenzyme.
  Appl Microbiol Biotechnol, 90, 227-234.  
21371502 Y.X.Si, S.J.Yin, D.Park, H.Y.Chung, L.Yan, Z.R.Lü, H.M.Zhou, J.M.Yang, G.Y.Qian, and Y.D.Park (2011).
Tyrosinase inhibition by isophthalic acid: kinetics and computational simulation.
  Int J Biol Macromol, 48, 700-704.  
20541942 L.Cerenius, S.Kawabata, B.L.Lee, M.Nonaka, and K.Söderhäll (2010).
Proteolytic cascades and their involvement in invertebrate immunity.
  Trends Biochem Sci, 35, 575-583.  
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