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2hi9
From Proteopedia
| 2hi9, resolution 2.30Å () | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Ligands: | , | ||||||||
| Gene: | SERPINA5 (Homo sapiens) | ||||||||
| Domains: | alpha-1-antitrypsin_like | ||||||||
| Related: | 1lq8 | ||||||||
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| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||||
Contents |
Crystal Structure of human native protein C inhibitor
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.
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
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
Disease
Known disease associated with this structure: Protein C inhibitor deficiency OMIM:[601841]
About this Structure
2HI9 is a 3 chains structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
Reference
- Li W, Adams TE, Kjellberg M, Stenflo J, Huntington JA. Structure of native protein C inhibitor provides insight into its multiple functions. J Biol Chem. 2007 May 4;282(18):13759-68. Epub 2007 Mar 2. PMID:17337440 doi:10.1074/jbc.M701074200
Page seeded by OCA on Wed Feb 18 01:13:00 2009
