1z8i
From Proteopedia
(New page: 200px<br /> <applet load="1z8i" size="450" color="white" frame="true" align="right" spinBox="true" caption="1z8i, resolution 2.00Å" /> '''Crystal structure o...) |
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| - | [[Image:1z8i.gif|left|200px]]<br /> | + | [[Image:1z8i.gif|left|200px]]<br /><applet load="1z8i" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1z8i" size=" | + | |
caption="1z8i, resolution 2.00Å" /> | caption="1z8i, resolution 2.00Å" /> | ||
'''Crystal structure of the thrombin mutant G193A bound to PPACK'''<br /> | '''Crystal structure of the thrombin mutant G193A bound to PPACK'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The oxyanion hole of serine proteases is formed by the backbone N atoms of | + | The oxyanion hole of serine proteases is formed by the backbone N atoms of the catalytic Ser-195 and Gly-193 and engages the backbone O atom of the P1 residue of substrate in an important H-bonding interaction. The energetic contribution of this interaction in the ground and transition states is presently unknown. Measurements of the individual rate constants defining the catalytic mechanism of substrate hydrolysis for wild-type thrombin and trypsin and their G193A and G193P mutants reveal that Gly-193 is required for optimal substrate binding and acylation. Crystal structures of the G193A and G193P mutants of thrombin bound to the active site inhibitor H-d-Phe-Pro-Arg-CH2Cl document the extent of perturbation induced by the replacement of Gly-193. The Ala mutant weakens the H-bonding interaction of the N atom of residue 193, whereas the Pro substitution abrogates it altogether with additional small shifts of the protein backbone. From the kinetic and structural data, we estimate that the H-bonding interaction in the oxyanion hole contributes a stabilization of the ground and transition states of > 1.5 kcal/mol but < 3.0 kcal/mol. These results shed light on a basic aspect of the enzyme-substrate interaction in the entire family of trypsin-like serine proteases. |
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1Z8I is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with NAG, ZN and NA as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Thrombin Thrombin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.5 3.4.21.5] Full crystallographic information is available from [http:// | + | 1Z8I is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=NAG:'>NAG</scene>, <scene name='pdbligand=ZN:'>ZN</scene> and <scene name='pdbligand=NA:'>NA</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Thrombin Thrombin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.5 3.4.21.5] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1Z8I OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Protein complex]] | [[Category: Protein complex]] | ||
[[Category: Thrombin]] | [[Category: Thrombin]] | ||
| - | [[Category: Bobofchak, K | + | [[Category: Bobofchak, K M.]] |
| - | [[Category: Cera, E | + | [[Category: Cera, E Di.]] |
| - | [[Category: Mathews, F | + | [[Category: Mathews, F S.]] |
| - | [[Category: Pineda, A | + | [[Category: Pineda, A O.]] |
[[Category: NA]] | [[Category: NA]] | ||
[[Category: NAG]] | [[Category: NAG]] | ||
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[[Category: thrombin]] | [[Category: thrombin]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:13:06 2008'' |
Revision as of 14:13, 21 February 2008
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Crystal structure of the thrombin mutant G193A bound to PPACK
Contents |
Overview
The oxyanion hole of serine proteases is formed by the backbone N atoms of the catalytic Ser-195 and Gly-193 and engages the backbone O atom of the P1 residue of substrate in an important H-bonding interaction. The energetic contribution of this interaction in the ground and transition states is presently unknown. Measurements of the individual rate constants defining the catalytic mechanism of substrate hydrolysis for wild-type thrombin and trypsin and their G193A and G193P mutants reveal that Gly-193 is required for optimal substrate binding and acylation. Crystal structures of the G193A and G193P mutants of thrombin bound to the active site inhibitor H-d-Phe-Pro-Arg-CH2Cl document the extent of perturbation induced by the replacement of Gly-193. The Ala mutant weakens the H-bonding interaction of the N atom of residue 193, whereas the Pro substitution abrogates it altogether with additional small shifts of the protein backbone. From the kinetic and structural data, we estimate that the H-bonding interaction in the oxyanion hole contributes a stabilization of the ground and transition states of > 1.5 kcal/mol but < 3.0 kcal/mol. These results shed light on a basic aspect of the enzyme-substrate interaction in the entire family of trypsin-like serine proteases.
Disease
Known diseases associated with this structure: Dysprothrombinemia OMIM:[176930], Hyperprothrombinemia OMIM:[176930], Hypoprothrombinemia OMIM:[176930]
About this Structure
1Z8I is a Protein complex structure of sequences from Homo sapiens with , and as ligands. Active as Thrombin, with EC number 3.4.21.5 Full crystallographic information is available from OCA.
Reference
Energetic and structural consequences of perturbing Gly-193 in the oxyanion hole of serine proteases., Bobofchak KM, Pineda AO, Mathews FS, Di Cera E, J Biol Chem. 2005 Jul 8;280(27):25644-50. Epub 2005 May 12. PMID:15890651
Page seeded by OCA on Thu Feb 21 16:13:06 2008
Categories: Homo sapiens | Protein complex | Thrombin | Bobofchak, K M. | Cera, E Di. | Mathews, F S. | Pineda, A O. | NA | NAG | ZN | Oxyanion hole | Serine protease
