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2ol2
From Proteopedia
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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. |
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| + | ==Disease== | ||
| + | Known diseases associated with this structure: Protein C inhibitor deficiency OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=601841 601841]] | ||
==About this Structure== | ==About this Structure== | ||
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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: Huntington, J | + | [[Category: Huntington, J A.]] |
[[Category: Li, W.]] | [[Category: Li, W.]] | ||
[[Category: GOL]] | [[Category: GOL]] | ||
[[Category: serpin]] | [[Category: serpin]] | ||
| - | ''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 18:19:39 2008'' |
Revision as of 16:19, 21 February 2008
|
High Resolution Structure of Native PCI in Space Group P21
Contents |
Overview
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
Known diseases associated with this structure: Protein C inhibitor deficiency OMIM:[601841]
About this Structure
2OL2 is a Single protein structure of sequence from Homo sapiens with as ligand. Full crystallographic information is available from OCA.
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 May 4;282(18):13759-68. Epub 2007 Mar 2. PMID:17337440
Page seeded by OCA on Thu Feb 21 18:19:39 2008
Categories: Homo sapiens | Single protein | Huntington, J A. | Li, W. | GOL | Serpin
