Document Detail


Crystal structure of zebrafish hatching enzyme 1 from the zebrafish Danio rerio.
MedLine Citation:
PMID:  20727360     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Fish hatching enzymes are zinc metalloproteases that digest the egg envelope (chorion) at the time of hatching. The crystal structure of zebrafish hatching enzyme 1 (ZHE1) has been solved at 1.10 Å resolution. ZHE1 is monomeric, is mitten shaped, and has a cleft at the center of the molecule. ZHE1 consists of three 3(10)-helices, three α-helices, and two β-sheets. The central cleft represents the active site of the enzyme that is crucial for substrate recognition and catalysis. Alanine-scanning mutagenesis of the two substrate peptides has shown that AspP1' contributes the most and that the residues at P4-P2' also contribute to the recognition of the major substrate peptide by ZHE1, whereas GluP3' and the hydrophobic residues at P4-P2, P2', and P5' contribute significantly to the recognition of the minor substrate peptide by ZHE1. Molecular models of these two substrate peptides bound to ZHE1 have been built based on the crystal structure of a transition-state analog inhibitor bound to astacin. In substrate-recognition models, the AspP1' in the major substrate peptide forms a salt bridge with Arg182 of ZHE1, while the GluP3' in the minor substrate peptide instead forms a salt bridge with Arg182. Thus, these two substrate peptides would be differently recognized by ZHE1. The shapes and electrostatic potentials of the substrate-binding clefts of ZHE1 and the structurally similar proteins astacin and bone morphogenetic protein 1 are significantly dissimilar due to different side chains, which would confer their distinctive substrate preferences.
Authors:
Akitoshi Okada; Kaori Sano; Koji Nagata; Shigeki Yasumasu; Jun Ohtsuka; Akihiro Yamamura; Keiko Kubota; Ichiro Iuchi; Masaru Tanokura
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-08-18
Journal Detail:
Title:  Journal of molecular biology     Volume:  402     ISSN:  1089-8638     ISO Abbreviation:  J. Mol. Biol.     Publication Date:  2010 Oct 
Date Detail:
Created Date:  2010-10-04     Completed Date:  2010-10-19     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  2985088R     Medline TA:  J Mol Biol     Country:  England    
Other Details:
Languages:  eng     Pagination:  865-78     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 Elsevier Ltd. All rights reserved.
Affiliation:
Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan.
Data Bank Information
Bank Name/Acc. No.:
PDB/3LQB
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Amino Acid Sequence
Amino Acid Substitution
Animals
Catalytic Domain
Crystallography, X-Ray
Metalloendopeptidases / chemistry*,  metabolism*
Models, Molecular
Molecular Sequence Data
Mutagenesis, Site-Directed
Protein Conformation
Protein Structure, Tertiary
Sequence Alignment
Zebrafish*
Chemical
Reg. No./Substance:
EC 3.4.24.-/Metalloendopeptidases; EC 3.4.24.12/envelysin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Co-Evolution of Antibody Stability and Vk CDR-L3 Canonical Structure.
Next Document:  Enzymes involved in osmolyte synthesis: How does oxidative stress affect osmoregulation in renal cel...