Address of Corresponding Author

Pancreatology 2006;6:117-122 (DOI: 10.1159/000090031)

  Key Words

• Pancreatic elastase
• Gene duplication
• Pseudogene
• Antitrypsin

  Abstract

Background: The archetypal mammalian elastase (ELA1) is not expressed in the human pancreas, because evolutionary mutations suppressed transcription of the ELA1 gene. Aims: In this study, we tested the theory that the unique duplication of the ELA2 gene in humans might compensate for the loss of ELA1. Methods: Recombinant ELA2A and ELA2B were expressed in Escherichia coli, and their activity was tested on Glt-Ala-Ala-Pro-Leu-p-nitroanilide, DQ elastin and bovine milk protein. Results: Surprisingly, recombinant ELA2B was completely devoid of proteolytic activity, while ELA2A readily hydrolyzed all three test substrates. Furthermore, ELA2A formed an SDS-resistant complex with ₁-antitrypsin, whereas ELA2B did not bind covalently to the inhibitor. Finally, chimeras and point mutations engineered between ELA2A and ELA2B revealed that multiple evolutionary mutations inactivated ELA2B. Conclusions: The results indicate that ELA2B is not an elastase enzyme and confirm that ELA2A is the major elastase in the human pancreas.

Copyright © 2006 S. Karger AG, Basel and IAP

  Author Contacts

Miklós Sahin-Tóth, MD
715 Albany Street, EVANS-4
Boston, MA 02118 (USA)
Tel. +1 617 414 1070, Fax +1 617 414 1041
E-Mail miklos@bu.edu

  Article Information

Received: April 20, 2005
Accepted after revision: July 25, 2005
Published online: December 1, 2005
Number of Print Pages : 6
Number of Figures : 4, Number of Tables : 0, Number of References : 15