Crystal structure of the inhibitor-free form of the serine protease kallikrein-4

Blake T. Riley, David E. Hoke, Sheena McGowan, Ashley M. Buckle

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Kallikrein 4 (KLK4) is a serine protease that is predominantly expressed in the prostate and is overexpressed in prostate cancer. As such, it has gained attention as an attractive target for prostate cancer therapeutics. Currently, only liganded structures of KLK4 exist in the Protein Data Bank. Until now, inferences about the subtle structural changes in KLK4 upon ligand binding have been made by comparison to other liganded forms, rather than to an apo form. In this study, an inhibitor-free form of KLK4 was crystallized. The crystals obtained belonged to space group P1, contained four molecules in the asymmetric unit and diffracted to 1.64 Å resolution. Interestingly, a nonstandard rotamer of the specificity-determining residue Asp189 was observed in all chains. This model will provide a useful unliganded structure for the future structure-guided design of KLK4 inhibitors.

Original languageEnglish
Pages (from-to)543-546
Number of pages4
JournalActa Crystallographica Section F: Structural Biology Communications
VolumeF75
DOIs
Publication statusPublished - Aug 2019

Keywords

  • Apo structure
  • Kallikrein-related peptidase 4
  • KLK4
  • Unliganded

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