2HI9

Crystal Structure of human native protein C inhibitor

Summary for 2HI9

• Entry DOI: 10.2210/pdb2hi9/pdb
• Related: 1LQ8
• Descriptor: Plasma serine protease inhibitor, CITRIC ACID, GLYCEROL, ... (4 entities in total)
• Functional Keywords: serpin, coagulation, haemostasis, thrombin inhibitor, activated protein c inhibitor, acrosin inhibitor, serine protease inhibitor, hydrolase inhibitor
• Biological source: Homo sapiens (human)
• Cellular location: Secreted: P05154
• Total number of polymer chains: 3
• Total formula weight: 123475.91

Authors

Li, W.,Adams, T.E.,Huntington, J.A. (deposition date: 2006-06-29, release date: 2007-03-13, Last modification date: 2024-03-13)

Primary citation

Li, W.,Adams, T.E.,Kjellberg, M.,Stenflo, J.,Huntington, J.A.
Structure of native protein C inhibitor provides insight into its multiple functions.
J.Biol.Chem., 282:13759-13768, 2007

PubMed Abstract: Protein C inhibitor (PCI) is a multifunctional serpin with wide ranging protease inhibitory functions, unique cofactor binding activities, and potential non-inhibitory functions akin to the hormone-transporting serpins. To gain insight into the molecular mechanisms utilized by PCI we developed a robust expression system in Escherichia coli and solved the crystal structure of PCI in its native state. The five monomers obtained from our two crystal forms provide an NMR-like ensemble revealing regions of inherent flexibility. The reactive center loop (RCL) of PCI is long and highly flexible with no evidence of hinge region incorporation into beta-sheet A, as seen for other heparin-binding serpins. We adapted an extrinsic fluorescence method for determining dissociation constants for heparin and find that the N-terminal tail of PCI and residues adjacent to helix H are not involved in heparin binding. The minimal heparin length capable of tight binding to PCI was determined to be chains of eight monosaccharide units. A large hydrophobic pocket occupied by hydrophobic crystal contacts was found in an analogous position to the hormone-binding site in thyroxine-binding globulin. In conclusion, the data presented here provide important insights into the mechanisms by which PCI exercises its multiple inhibitory and non-inhibitory functions.

PubMed: 17337440
DOI: 10.1074/jbc.M701074200

Experimental method

X-RAY DIFFRACTION (2.3 Å)