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PDBsum entry 2ayw
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References listed in PDB file
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Key reference
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Title
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Structure of the complex of trypsin with a highly potent synthetic inhibitor at 0.97 a resolution.
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Authors
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M.Sherawat,
P.Kaur,
M.Perbandt,
C.Betzel,
W.A.Slusarchyk,
G.S.Bisacchi,
C.Chang,
B.L.Jacobson,
H.M.Einspahr,
T.P.Singh.
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Ref.
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Acta Crystallogr D Biol Crystallogr, 2007,
63,
500-507.
[DOI no: ]
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PubMed id
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Abstract
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The structure of the complex formed between bovine beta-trypsin and the highly
potent synthetic inhibitor
2-{3'-[5'-methoxy-2'-(N-p-diaminomethylphenyl)amido]-1'-pyrido}-5-(N-2''-t-butylethanol)amidobenzoic
acid (C(28)H(32)N(5)O(6)) has been determined at 0.97 A resolution. X-ray
intensity data were collected to 0.97 A under cryocooled conditions. The
structure was refined anisotropically using REFMAC5 and SHELX-97 to R(cryst)
factors of 13.4 and 12.6% and R(free) factors of 15.7 and 16.3%, respectively.
Several regions of the main chain and side chains that have not been previously
observed were clearly defined in the present structure. H atoms are indicated as
significant peaks in an |F(o) - F(c)| difference map, which accounts for an
estimated 35% of all H atoms at the 2.5sigma level. The C, N and O atoms are
definitively differentiated in the electron-density maps. The amido part of the
inhibitor occupies the specificity pocket and the remainder fills the remaining
part of the ligand-binding cleft and interacts with the enzyme through an
extensive network of hydrogen bonds. The inhibitor distorts the stereochemistry
of the catalytic triad, Ser195-His57-Asp102, thereby blocking the proton-relay
process of the active site by preventing the formation of the crucial hydrogen
bond between His57 N(delta1) and Asp102 O(delta1).
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Figure 1.
Figure 1 The |F[o] - F[c]| map contoured at 2.5  showing
the electron densities for two molecules of the inhibitor
2-{3'-[5'-methoxy-2'-(N-p-diaminomethylphenyl)amido]-1'-pyrido}-5-(N-2´´-t-butylethanol)amidobenzoic
acid (ONO), benzamidine (BDN), glycerol (GOL) and
2-(N-morpholino)ethanesulfonic acid (MES). ONO1 is shown in
yellow, whereas ONO2 is indicated in green. The figure was drawn
with PyMOL (DeLano, 2002[DeLano, W. L. (2002). The PyMOL
Molecular Graphics System. DeLano Scientific, San Carlos, CA,
USA.]).
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Figure 3.
Figure 3 |2F[o] - F[c]| electron-density map contoured at 1.2
showing
disordered residues with more than one conformation for the side
chains: (a) Ser37, (b) Asp165, (c) Ser113, (d) Lys60, (e) Arg117.
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The above figures are
reprinted
by permission from the IUCr:
Acta Crystallogr D Biol Crystallogr
(2007,
63,
500-507)
copyright 2007.
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