3er5
From Proteopedia
(New page: 200px<br /><applet load="3er5" size="450" color="white" frame="true" align="right" spinBox="true" caption="3er5, resolution 1.8Å" /> '''THE ACTIVE SITE OF AS...) |
|||
| Line 1: | Line 1: | ||
| - | [[Image:3er5.jpg|left|200px]]<br /><applet load="3er5" size=" | + | [[Image:3er5.jpg|left|200px]]<br /><applet load="3er5" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="3er5, resolution 1.8Å" /> | caption="3er5, resolution 1.8Å" /> | ||
'''THE ACTIVE SITE OF ASPARTIC PROTEINASES'''<br /> | '''THE ACTIVE SITE OF ASPARTIC PROTEINASES'''<br /> | ||
==Overview== | ==Overview== | ||
| - | H-189, a synthetic human renin inhibitor, and pepstatin A, a naturally | + | H-189, a synthetic human renin inhibitor, and pepstatin A, a naturally occurring inhibitor of aspartic proteinases, have been co-crystallized with the fungal aspartic proteinase endothiapepsin (EC 3.4.23.6). H-189 [Pro-His-Pro-Phe-His-Sta-(statyl)-Val-Ile-His-Lys] is an analogue of human angiotensinogen. Pepstatin A [Iva(isovaleryl)-Val-Val-Sta-Ala-Sta] is a blocked pentapeptide which inhibits many aspartic proteinases. The structures of the complexes have been determined by X-ray diffraction and refined to crystallographic R-factors of 0.15 and 0.16 at resolutions of 0.18 nm (1.8 A) and 0.2 nm (2.0 A) respectively. H-189 is in an extended conformation, in which the statine residue is a dipeptide analogue of P1 and P'1 as indicated by the conformation and network of contacts and hydrogen bonds. Pepstatin A has an extended conformation to the P'2 alanine residue, but the leucyl side chain of the terminal statine residue binds back into the S'1 subsite, and an inverse gamma-turn occurs between P'1 and P'3. The hydroxy moiety of the statine at P1 in both complexes displaces the solvent molecule that hydrogen-bonds with the catalytic aspartate residues (32 and 215) in the native enzyme. Solvent molecules originally present in the native structure at the active site are displaced on inhibitor binding (12 when pepstatin A binds; 16 when H-189 binds). |
==About this Structure== | ==About this Structure== | ||
| - | 3ER5 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Cryphonectria_parasitica Cryphonectria parasitica]. Active as [http://en.wikipedia.org/wiki/Hydrolase Hydrolase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.103, 3.4.23.18, 3.4.23.28 and 3.4.23.30 3.4.21.103, 3.4.23.18, 3.4.23.28 and 3.4.23.30] Full crystallographic information is available from [http:// | + | 3ER5 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Cryphonectria_parasitica Cryphonectria parasitica]. Active as [http://en.wikipedia.org/wiki/Hydrolase Hydrolase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.103, 3.4.23.18, 3.4.23.28 and 3.4.23.30 3.4.21.103, 3.4.23.18, 3.4.23.28 and 3.4.23.30] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3ER5 OCA]. |
==Reference== | ==Reference== | ||
| Line 15: | Line 15: | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
[[Category: Bailey, D.]] | [[Category: Bailey, D.]] | ||
| - | [[Category: Blundell, T | + | [[Category: Blundell, T L.]] |
[[Category: Cooper, J.]] | [[Category: Cooper, J.]] | ||
[[Category: Szelke, M.]] | [[Category: Szelke, M.]] | ||
| Line 21: | Line 21: | ||
[[Category: hydrolase (acid proteinase)]] | [[Category: hydrolase (acid proteinase)]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 19:09:20 2008'' |
Revision as of 17:09, 21 February 2008
|
THE ACTIVE SITE OF ASPARTIC PROTEINASES
Overview
H-189, a synthetic human renin inhibitor, and pepstatin A, a naturally occurring inhibitor of aspartic proteinases, have been co-crystallized with the fungal aspartic proteinase endothiapepsin (EC 3.4.23.6). H-189 [Pro-His-Pro-Phe-His-Sta-(statyl)-Val-Ile-His-Lys] is an analogue of human angiotensinogen. Pepstatin A [Iva(isovaleryl)-Val-Val-Sta-Ala-Sta] is a blocked pentapeptide which inhibits many aspartic proteinases. The structures of the complexes have been determined by X-ray diffraction and refined to crystallographic R-factors of 0.15 and 0.16 at resolutions of 0.18 nm (1.8 A) and 0.2 nm (2.0 A) respectively. H-189 is in an extended conformation, in which the statine residue is a dipeptide analogue of P1 and P'1 as indicated by the conformation and network of contacts and hydrogen bonds. Pepstatin A has an extended conformation to the P'2 alanine residue, but the leucyl side chain of the terminal statine residue binds back into the S'1 subsite, and an inverse gamma-turn occurs between P'1 and P'3. The hydroxy moiety of the statine at P1 in both complexes displaces the solvent molecule that hydrogen-bonds with the catalytic aspartate residues (32 and 215) in the native enzyme. Solvent molecules originally present in the native structure at the active site are displaced on inhibitor binding (12 when pepstatin A binds; 16 when H-189 binds).
About this Structure
3ER5 is a Protein complex structure of sequences from Cryphonectria parasitica. Active as Hydrolase, with EC number 3.4.23.18, 3.4.23.28 and 3.4.23.30 3.4.21.103, 3.4.23.18, 3.4.23.28 and 3.4.23.30 Full crystallographic information is available from OCA.
Reference
X-ray-crystallographic studies of complexes of pepstatin A and a statine-containing human renin inhibitor with endothiapepsin., Bailey D, Cooper JB, Veerapandian B, Blundell TL, Atrash B, Jones DM, Szelke M, Biochem J. 1993 Jan 15;289 ( Pt 2):363-71. PMID:8424781
Page seeded by OCA on Thu Feb 21 19:09:20 2008
