3F1S

Crystal structure of Protein Z complexed with protein Z-dependent inhibitor

Summary for 3F1S

• Entry DOI: 10.2210/pdb3f1s/pdb
• Descriptor: Protein Z-dependent protease inhibitor, Vitamin K-dependent protein Z, CHLORIDE ION, ... (7 entities in total)
• Functional Keywords: pz, zpi, complex, serpin, protease inhibitor, protease, glycoprotein, secreted, serine protease inhibitor, blood coagulation, cleavage on pair of basic residues, egf-like domain, gamma-carboxyglutamic acid, hydroxylation, serine protease homolog, hydrolase inhibitor-hydrolase complex, hydrolase inhibitor/hydrolase
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 2
• Total formula weight: 76582.52

Authors

Zhou, A. (deposition date: 2008-10-28, release date: 2009-06-30, Last modification date: 2024-10-30)

Primary citation

Wei, Z.,Yan, Y.,Carrell, R.W.,Zhou, A.
Crystal structure of protein Z-dependent inhibitor complex shows how protein Z functions as a cofactor in the membrane inhibition of factor X.
Blood, 2009

PubMed Abstract: Protein Z (PZ) binds to PZ-dependent inhibitor (ZPI) and accelerates the inhibition of the coagulation protease, activated factor X (FXa), in the presence of phospholipids and Ca2+. A 2.3A resolution crystal structure of PZ complexed with ZPI shows that ZPI is a typical serine protease inhibitor and that PZ has a serine protease fold with distorted oxyanion hole and S1 pocket. The 2 molecules bind with fully complementary surfaces spanning over 2400A(2) and involving extensive ionic and hydrophobic interactions. ZPI has an unusual shutter region with a negatively charged residue buried within the hydrophobic core of the molecule. This unique Asp(213) is critical in maintaining the balanced metastability required for optimal protease inhibition, especially when PZ is bound, with its replacement with Asn resulting in increased thermal stability, but decreased efficiency of protease inhibition. The structure of ZPI shows negatively and positively charged surfaces on top of the molecule, in keeping with mutagenesis studies in this work indicating exosite interactions with FXa when it docks on top of ZPI. As modeled in this study, the gamma-carboxy-glutamic acid-containing domains of PZ and FXa enable them to bind to the same phospholipid surfaces on platelet and other membranes, with optimal proximity for the inhibition of FXa by the complexed ZPI.

PubMed: 19528533
DOI: 10.1182/blood-2009-04-210021

Experimental method

X-RAY DIFFRACTION (2.3 Å)