2hi9: Difference between revisions
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==Overview== | ==Overview== | ||
Protein C inhibitor (PCI) is a multifunctional serpin with wide | 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. | ||
==Disease== | ==Disease== | ||
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==Reference== | ==Reference== | ||
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 | 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 May 4;282(18):13759-68. Epub 2007 Mar 2. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17337440 17337440] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Adams, T | [[Category: Adams, T E.]] | ||
[[Category: Huntington, J | [[Category: Huntington, J A.]] | ||
[[Category: Li, W.]] | [[Category: Li, W.]] | ||
[[Category: CIT]] | [[Category: CIT]] | ||
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[[Category: thrombin inhibitor]] | [[Category: thrombin inhibitor]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:42:11 2008'' | ||
Revision as of 18:42, 21 February 2008
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Crystal Structure of human native protein C inhibitor
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. 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.
DiseaseDisease
Known diseases associated with this structure: Protein C inhibitor deficiency OMIM:[601841]
About this StructureAbout this Structure
2HI9 is a Single protein structure of sequence from Homo sapiens with and as ligands. 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 May 4;282(18):13759-68. Epub 2007 Mar 2. PMID:17337440
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