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PDBsum entry 1btu
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Serine protease
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PDB id
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1btu
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References listed in PDB file
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Key reference
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Title
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Inhibition of elastase by n-Sulfonylaryl beta-Lactams: anatomy of a stable acyl-Enzyme complex.
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Authors
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R.C.Wilmouth,
N.J.Westwood,
K.Anderson,
W.Brownlee,
T.D.Claridge,
I.J.Clifton,
G.J.Pritchard,
R.T.Aplin,
C.J.Schofield.
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Ref.
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Biochemistry, 1998,
37,
17506-17513.
[DOI no: ]
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PubMed id
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Abstract
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beta-Lactam inhibitors of transpeptidase enzymes involved in cell wall
biosynthesis remain among the most important therapeutic agents in clinical use.
beta-Lactams have more recently been developed as inhibitors of serine proteases
including elastase. All therapeutically useful beta-lactam inhibitors operate
via mechanisms resulting in the formation of hydrolytically stable acyl-enzyme
complexes. Presently, it is difficult to predict which beta-lactams will form
stable acyl-enzyme complexes with serine enzymes. Further, the factors that
result in the seemingly special nature of beta-lactams versus other acylating
agents are unclear-if indeed they exist. Here we present the 1.6 A resolution
crystal structure of a stable acyl-enzyme complex formed between porcine
pancreatic elastase and a representative monocyclic beta-lactam, which forms a
simple acyl-enzyme. The structure shows that the ester carbonyl is not located
within the oxyanion hole and the "hydrolytic" water is displaced. Combined with
additional kinetic and mass spectrometric data, the structure allows the
rationalization of the low degree of hydrolytic lability observed for the
beta-lactam-derived acyl-enzyme complex.
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Secondary reference #1
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Title
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Structure of a specific acyl-Enzyme complex formed between beta-Casomorphin-7 and porcine pancreatic elastase.
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Authors
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R.C.Wilmouth,
I.J.Clifton,
C.V.Robinson,
P.L.Roach,
R.T.Aplin,
N.J.Westwood,
J.Hajdu,
C.J.Schofield.
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Ref.
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Nat Struct Biol, 1997,
4,
456-462.
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PubMed id
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Secondary reference #2
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Title
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Inhibition of human serine proteases by substituted 2-Azetidinones.
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Authors
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W.B.Knight,
R.Chabin,
B.Green.
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Ref.
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Arch Biochem Biophys, 1992,
296,
704-708.
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PubMed id
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Secondary reference #3
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Title
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Specificity, Stability, And potency of monocyclic beta-Lactam inhibitors of human leucocyte elastase.
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Authors
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W.B.Knight,
B.G.Green,
R.M.Chabin,
P.Gale,
A.L.Maycock,
H.Weston,
D.W.Kuo,
W.M.Westler,
C.P.Dorn,
P.E.Finke.
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Ref.
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Biochemistry, 1992,
31,
8160-8170.
[DOI no: ]
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PubMed id
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Secondary reference #4
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Title
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Monocyclic beta-Lactam inhibitors of human leukocyte elastase
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Authors
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R.A.Firestone,
P.L.Barker,
J.M.Pisano,
B.M.Ashe,
M.E.Dahlgren.
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Ref.
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tetrahedron, 1990,
46,
2255.
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Secondary reference #5
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Title
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Structure of native porcine pancreatic elastase at 1.65 a resolutions.
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Authors
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E.Meyer,
G.Cole,
R.Radhakrishnan,
O.Epp.
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Ref.
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Acta Crystallogr B, 1988,
44,
26-38.
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PubMed id
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