PDBsum entry 3f1s

Hydrolase inhibitor/hydrolase

PDB id: 3f1s

Contents

Protein chains

385 a.a. *

259 a.a. *

Ligands

EDO

FLC

NAG

Metals

_CL

Waters ×82

* Residue conservation analysis

PDB id:

3f1s

Name:

Hydrolase inhibitor/hydrolase

Title:

Crystal structure of protein z complexed with protein z-dependent inhibitor

Structure:

Protein z-dependent protease inhibitor. Chain: a. Fragment: egf2 and protease domain. Synonym: pz-dependent protease inhibitor, pzi, serpin a10. Engineered: yes. Vitamin k-dependent protein z. Chain: b. Fragment: unp residues 125-400. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: serpina10, unq707/pro1358, zpi. Expressed in: escherichia coli. Expression_system_taxid: 562. Gene: proz, pz. Expression_system_cell: hek293 cells.

Resolution:

2.30Å R-factor: 0.227 R-free: 0.271

Authors:

A.Zhou

Key ref:

Z.Wei et al. (2009). Crystal structure of protein Z-dependent inhibitor complex shows how protein Z functions as a cofactor in the membrane inhibition of factor X. Blood, 114, 3662-3667. PubMed id: 19528533

Date:

28-Oct-08 Release date: 30-Jun-09

Protein chain

Q9UK55  (ZPI_HUMAN) -  Protein Z-dependent protease inhibitor from Homo sapiens

Seq: 444 a.a.

Struc: 385 a.a.

Protein chain

P22891  (PROZ_HUMAN) -  Vitamin K-dependent protein Z from Homo sapiens

Seq: 400 a.a.

Struc: 259 a.a.

Blood 114:3662-3667 (2009)

PubMed id: 19528533

Crystal structure of protein Z-dependent inhibitor complex shows how protein Z functions as a cofactor in the membrane inhibition of factor X.

Z.Wei, Y.Yan, R.W.Carrell, A.Zhou.

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.