 |
PDBsum entry 5er2
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Hydrolase/hydrolase inhibitor
|
PDB id
|
|
|
|
5er2
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
Contents |
 |
|
|
|
|
|
|
|
|
|
|
|
|
* Residue conservation analysis
|
|
|
|
|
References listed in PDB file
|
|
|
Key reference
|
|
|
Title
|
|
High-Resolution X-Ray diffraction study of the complex between endothiapepsin and an oligopeptide inhibitor: the analysis of the inhibitor binding and description of the rigid body shift in the enzyme.
|
|
|
Authors
|
|
A.Sali,
B.Veerapandian,
J.B.Cooper,
S.I.Foundling,
D.J.Hoover,
T.L.Blundell.
|
|
|
Ref.
|
|
Embo J, 1989,
8,
2179-2188.
|
|
|
PubMed id
|
|
|
|
|
|
Abstract
|
|
|
The conformation of the synthetic renin inhibitor CP-69,799, bound to the active
site of the fungal aspartic proteinase endothiapepsin (EC 3.4.23.6), has been
determined by X-ray diffraction at 1.8 A resolution and refined to the
crystallographic R factor of 16%. CP-69,799 is an oligopeptide transition--state
analogue inhibitor that contains a new dipeptide isostere at the P1-P1'
position. This dipeptide isostere is a nitrogen analogue of the well-explored
hydroxyethylene dipeptide isostere, wherein the tetrahedral P1' C alpha atom has
been replaced by trigonal nitrogen. The inhibitor binds in the extended
conformation, filling S4 to S3' pockets, with hydroxyl group of the P1 residue
positioned symmetrically between the two catalytic aspartates of the enzyme.
Interactions between the inhibitor and the enzyme include 12 hydrogen bonds and
extensive van der Waals contacts in all the pockets, except for S3'. The crystal
structure reveals a bifurcated orientation of the P2 histidine side chain and an
interesting relative rotation of the P3 phenyl ring to accommodate the
cyclohexyl side chain at P1. The binding of the inhibitor to the enzyme, while
producing no large distortions in the enzyme active site cleft, results in small
but significant change in the relative orientation of the two endothiapepsin
domains. This structural change may represent the action effected by the
proteinase as it distorts its substrate towards the transition state for
proteolytic cleavage.
|
|
|
Secondary reference #1
|
|
|
Title
|
|
The active site of aspartic proteinases.
|
|
|
Authors
|
|
L.Pearl,
T.Blundell.
|
|
|
Ref.
|
|
Febs Lett, 1984,
174,
96.
|
|
|
PubMed id
|
|
|
|
|
|
|
|
|
Secondary reference #2
|
|
|
Title
|
|
Active site of acid proteinases
|
|
|
Authors
|
|
T.L.Blundell,
H.B.Jones,
G.Khan,
G.Taylor,
T.S.Sewell,
L.H.Pearl,
S.P.Wood.
|
|
|
Ref.
|
|
proc febs meet, 1979,
60,
281.
|
|
|
|
Secondary reference #3
|
|
|
Title
|
|
The three-Dimensional structure of acid proteinases
|
|
|
Authors
|
|
T.L.Blundell,
J.A.Jenkins,
G.Khan,
P.Roy Chowdhury,
T.Sewell,
I.J.Tickle,
E.A.Wood.
|
|
|
Ref.
|
|
proc febs meet, 1979,
52,
81.
|
|
|
|
Secondary reference #4
|
|
|
Title
|
|
Four-Fold structural repeat in the acid proteases.
|
|
|
Authors
|
|
T.L.Blundell,
B.T.Sewell,
A.D.Mclachlan.
|
|
|
Ref.
|
|
Biochim Biophys Acta, 1979,
580,
24-31.
[DOI no: ]
|
|
|
PubMed id
|
|
|
|
|
|
|
|
|
Secondary reference #5
|
|
|
Title
|
|
Structural evidence for gene duplication in the evolution of the acid proteases.
|
|
|
Authors
|
|
J.Tang,
M.N.James,
I.N.Hsu,
J.A.Jenkins,
T.L.Blundell.
|
|
|
Ref.
|
|
Nature, 1978,
271,
618-621.
|
|
|
PubMed id
|
|
|
|
|
|
|
|
|
Secondary reference #6
|
|
|
Title
|
|
Homology among acid proteases: comparison of crystal structures at 3a resolution of acid proteases from rhizopus chinensis and endothia parasitica.
|
|
|
Authors
|
|
E.Subramanian,
I.D.Swan,
M.Liu,
D.R.Davies,
J.A.Jenkins,
I.J.Tickle,
T.L.Blundell.
|
|
|
Ref.
|
|
Proc Natl Acad Sci U S A, 1977,
74,
556-559.
[DOI no: ]
|
|
|
PubMed id
|
|
|
|
|
|
|
|
|
Secondary reference #7
|
|
|
Title
|
|
X-Ray analysis and circular dichroism of the acid protease from endothia parasitica and chymosin.
|
|
|
Authors
|
|
J.Jenkins,
I.Tickle,
T.Sewell,
L.Ungaretti,
A.Wollmer,
T.Blundell.
|
|
|
Ref.
|
|
Adv Exp Med Biol, 1977,
95,
43-60.
|
|
|
PubMed id
|
|
|
|
|
|
|
|
|
|
|
|
|
