1epo: Difference between revisions

Revision as of 15:22, 2 May 2008

DIRECT OBSERVATION BY X-RAY ANALYSIS OF THE TETRAHEDRAL "INTERMEDIATE" OF ASPARTIC PROTEINASES

OverviewOverview

We report the X-ray analysis at 2.0 A resolution for crystals of the aspartic proteinase endothiapepsin (EC 3.4.23.6) complexed with a potent difluorostatone-containing tripeptide renin inhibitor (CP-81,282). The scissile bond surrogate, an electrophilic ketone, is hydrated in the complex. The pro-(R) (statine-like) hydroxyl of the tetrahedral carbonyl hydrate is hydrogen-bonded to both active-site aspartates 32 and 215 in the position occupied by a water in the native enzyme. The second hydroxyl oxygen of the hydrate is hydrogen-bonded only to the outer oxygen of Asp 32. These experimental data provide a basis for a model of the tetrahedral intermediate in aspartic proteinase-mediated cleavage of the amide bond. This indicates a mechanism in which Asp 32 is the proton donor and Asp 215 carboxylate polarizes a bound water for nucleophilic attack. The mechanism involves a carboxylate (Asp 32) that is stabilized by extensive hydrogen bonding, rather than an oxyanion derivative of the peptide as in serine proteinase catalysis.

About this StructureAbout this Structure

1EPO is a Single protein structure. Full crystallographic information is available from OCA.

ReferenceReference

Direct observation by X-ray analysis of the tetrahedral "intermediate" of aspartic proteinases., Veerapandian B, Cooper JB, Sali A, Blundell TL, Rosati RL, Dominy BW, Damon DB, Hoover DJ, Protein Sci. 1992 Mar;1(3):322-8. PMID:1304340 Page seeded by OCA on Fri May 2 15:22:56 2008

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

@@ Line 1: / Line 1: @@
 [[Image:1epo.jpg|left|200px]]
- {{Structure
+<!--
-|PDB= 1epo |SIZE=350|CAPTION= <scene name='initialview01'>1epo</scene>, resolution 2.0&Aring;
+The line below this paragraph, containing "STRUCTURE_1epo", creates the "Structure Box" on the page.
-|SITE=
+You may change the PDB parameter (which sets the PDB file loaded into the applet)
-|LIGAND= <scene name='pdbligand=CHF:CYCLOHEXYLFLUOROSTATONE'>CHF</scene>, <scene name='pdbligand=MOR:N-CARBONYLMORPHOLINE'>MOR</scene>, <scene name='pdbligand=NLE:NORLEUCINE'>NLE</scene>, <scene name='pdbligand=NME:METHYLAMINE'>NME</scene>
+or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-|ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Endothiapepsin Endothiapepsin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.23.22 3.4.23.22] </span>
+or leave the SCENE parameter empty for the default display.
-|GENE=
+-->
-|DOMAIN=
+{{STRUCTURE_1epo|  PDB=1epo  |  SCENE=  }}
-|RELATEDENTRY=
-|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1epo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1epo OCA], [http://www.ebi.ac.uk/pdbsum/1epo PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1epo RCSB]</span>
-}}
 '''DIRECT OBSERVATION BY X-RAY ANALYSIS OF THE TETRAHEDRAL "INTERMEDIATE" OF ASPARTIC PROTEINASES'''
@@ Line 19: / Line 16: @@
 ==About this Structure==
-EPO is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/ ]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1EPO OCA].
+EPO is a [[Single protein]] structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1EPO OCA].
 ==Reference==
@@ Line 28: / Line 25: @@
 [[Category: Cooper, J B.]]
 [[Category: Veerapandian, B.]]
-[[Category: hydrolase(acid proteinase)]]
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May  2 15:22:56 2008''
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 20:07:16 2008''