Sandbox Reserved 596: Difference between revisions

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PZ is a single-chain protein with a N-terminal domain rich in γ-carboxyglutamic acids (Gla), two epidermal growth factor-like (EGF) domains and a C-terminal serine protease-like domain and has a molecular weight of 62 kDa. PZ genetically and structurally mimics other factors of the coagulation cascade but it is not a catalyticaly active enzyme. PZ is not like the other vitamin k-dependent coagulation factors because it does not have an active center, thus it lacks the Ser (S195) and His (H57) of the catalytic triad needed for the active site of serine proteases, like the coagulation factors VII, IX, X, and protein C. PZ's 360 amino acid sequence is N-terminally analogous to the serine protease coagulation factors, whose similarly composed genes are found clustered together along with PROZ on chromosome 13. PZ is 33% homologous in amino acid sequence to the coagulation factor it aids in inhibiting, factor Xa (FXa). PZ's binding interface is similar to that of thrombin, an anionic heparin binding site named exocite II.

The crystal structure of PZ shows a serine fold with a distorted oxyanion hole and S1 packet. The two EGF domains in PZ are closely drawn to the C-terminal serine protease-like domain. PZ is found in circulation as a complex with protein Z-dependent protease inhibitor (ZPI). The crystal structure of ZPI shows a serpin fold, with 3 central β-sheets, and a catalytic active center. ZPI has a negatively charged Asp213 residue in a hydrophobic core, which gives it maximum inhibition. Ionic and hydrophobic ~~nteractions~~ between the PZ's C-terminal along with its two neighboring EGF serves as a ZPI binding site while its N-terminal serves as a binding site to the membranous phospholipids. The PZ's N-terminal Gla domain is stabilized by the available calcium ions as it binds to the FXa and phospholipid hyprophobic loops.

The crystal structure of PZ shows a serine fold with a distorted oxyanion hole and S1 packet. The two EGF domains in PZ are closely drawn to the C-terminal serine protease-like domain. PZ is found in circulation as a complex with protein Z-dependent protease inhibitor (ZPI). The crystal structure of ZPI shows a serpin fold, with 3 central β-sheets, and a catalytic active center. ZPI has a negatively charged Asp213 residue in a hydrophobic core, which gives it maximum inhibition. Ionic and hydrophobic interactions between the PZ's C-terminal along with its two neighboring EGF serves as a ZPI binding site while its N-terminal serves as a binding site to the membranous phospholipids. The PZ's N-terminal Gla domain is stabilized by the available calcium ions as it binds to the FXa and phospholipid hyprophobic loops.

Sandbox Reserved 596: Difference between revisions

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Revision as of 03:25, 21 April 2013 view source Student (talk \| contribs) students 33,923 edits No edit summary ← Older edit		Revision as of 05:51, 21 April 2013 view source Student (talk \| contribs) students 33,923 edits No edit summary Newer edit →
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	PZ is a single-chain protein with a N-terminal domain rich in γ-carboxyglutamic acids (Gla), two epidermal growth factor-like (EGF) domains and a C-terminal serine protease-like domain and has a molecular weight of 62 kDa. PZ genetically and structurally mimics other factors of the coagulation cascade but it is not a catalyticaly active enzyme. PZ is not like the other vitamin k-dependent coagulation factors because it does not have an active center, thus it lacks the Ser (S195) and His (H57) of the catalytic triad needed for the active site of serine proteases, like the coagulation factors VII, IX, X, and protein C. PZ's 360 amino acid sequence is N-terminally analogous to the serine protease coagulation factors, whose similarly composed genes are found clustered together along with PROZ on chromosome 13. PZ is 33% homologous in amino acid sequence to the coagulation factor it aids in inhibiting, factor Xa (FXa). PZ's binding interface is similar to that of thrombin, an anionic heparin binding site named exocite II.		PZ is a single-chain protein with a N-terminal domain rich in γ-carboxyglutamic acids (Gla), two epidermal growth factor-like (EGF) domains and a C-terminal serine protease-like domain and has a molecular weight of 62 kDa. PZ genetically and structurally mimics other factors of the coagulation cascade but it is not a catalyticaly active enzyme. PZ is not like the other vitamin k-dependent coagulation factors because it does not have an active center, thus it lacks the Ser (S195) and His (H57) of the catalytic triad needed for the active site of serine proteases, like the coagulation factors VII, IX, X, and protein C. PZ's 360 amino acid sequence is N-terminally analogous to the serine protease coagulation factors, whose similarly composed genes are found clustered together along with PROZ on chromosome 13. PZ is 33% homologous in amino acid sequence to the coagulation factor it aids in inhibiting, factor Xa (FXa). PZ's binding interface is similar to that of thrombin, an anionic heparin binding site named exocite II.

	The crystal structure of PZ shows a serine fold with a distorted oxyanion hole and S1 packet. The two EGF domains in PZ are closely drawn to the C-terminal serine protease-like domain. PZ is found in circulation as a complex with protein Z-dependent protease inhibitor (ZPI). The crystal structure of ZPI shows a serpin fold, with 3 central β-sheets, and a catalytic active center. ZPI has a negatively charged Asp213 residue in a hydrophobic core, which gives it maximum inhibition. Ionic and hydrophobic ~~nteractions~~ between the PZ's C-terminal along with its two neighboring EGF serves as a ZPI binding site while its N-terminal serves as a binding site to the membranous phospholipids. The PZ's N-terminal Gla domain is stabilized by the available calcium ions as it binds to the FXa and phospholipid hyprophobic loops.		The crystal structure of PZ shows a serine fold with a distorted oxyanion hole and S1 packet. The two EGF domains in PZ are closely drawn to the C-terminal serine protease-like domain. PZ is found in circulation as a complex with protein Z-dependent protease inhibitor (ZPI). The crystal structure of ZPI shows a serpin fold, with 3 central β-sheets, and a catalytic active center. ZPI has a negatively charged Asp213 residue in a hydrophobic core, which gives it maximum inhibition. Ionic and hydrophobic interactions between the PZ's C-terminal along with its two neighboring EGF serves as a ZPI binding site while its N-terminal serves as a binding site to the membranous phospholipids. The PZ's N-terminal Gla domain is stabilized by the available calcium ions as it binds to the FXa and phospholipid hyprophobic loops.