2ol2
High Resolution Structure of Native PCI in Space Group P21
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OverviewOverview
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. In order to gain insight into the molecular mechanisms utilized, by PCI we developed a robust expression system in E. 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.
About this StructureAbout this Structure
2OL2 is a Single protein structure of sequence from Homo sapiens with as ligand. Full crystallographic information is available from OCA.
ReferenceReference
Structure of native protein C inhibitor provides insight into its multiple functions., Li W, Adams TE, Kjellberg M, Stenflo J, Huntington JA, J Biol Chem. 2007 Mar 2;. PMID:17337440
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