4Z2A

Crystal structure of unglycosylated apo human furin @1.89A

Summary for 4Z2A

• Entry DOI: 10.2210/pdb4z2a/pdb
• Related: 1P8J 4OMC
• Descriptor: Furin, CALCIUM ION, PHOSPHATE ION, ... (5 entities in total)
• Functional Keywords: unglycosylated, apo, serine proteinase, hydrolase
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 50917.87

Authors

Gampe, R.T.,Pearce, K.,Reid, R. (deposition date: 2015-03-29, release date: 2016-05-04, Last modification date: 2026-02-11)

Primary citation

Pearce, K.H.,Overton, L.K.,Gampe, R.T.,Barrett, G.B.,Taylor, J.D.,McKee, D.D.,Campobasso, N.,Nolte, R.T.,Reid, R.A.
BacMam production and crystal structure of nonglycosylated apo human furin at 1.89 angstrom resolution.
Acta Crystallogr.,Sect.F, 75:239-245, 2019

PubMed Abstract: Furin, also called proprotein convertase subtilisin/kexin 3 (PCSK3), is a calcium-dependent serine endoprotease that processes a wide variety of proproteins involved in cell function and homeostasis. Dysregulation of furin has been implicated in numerous disease states, including cancer and fibrosis. Mammalian cell expression of the furin ectodomain typically produces a highly glycosylated, heterogeneous protein, which can make crystallographic studies difficult. Here, the expression and purification of nonglycosylated human furin using the BacMam technology and site-directed mutagenesis of the glycosylation sites is reported. Nonglycosylated furin produced using this system retains full proteolytic activity indistinguishable from that of the glycosylated protein. Importantly, the nonglycosylated furin protein reliably forms extremely durable apo crystals that diffract to high resolution. These crystals can be soaked with a wide variety of inhibitors to enable a structure-guided drug-discovery campaign.

PubMed: 30950824
DOI: 10.1107/S2053230X19001419

Experimental method

X-RAY DIFFRACTION (1.89 Å)