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PDBsum entry 4thn
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Hydrolase/hydrolase inhibitor
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PDB id
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4thn
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Contents |
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* Residue conservation analysis
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PDB id:
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| Name: |
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Hydrolase/hydrolase inhibitor
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Title:
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The crystal structure of alpha-thrombin-hirunorm iv complex reveals a novel specificity site recognition mode.
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Structure:
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Alpha-thrombin. Chain: l. Alpha-thrombin. Chain: h. Hirunorm iv. Chain: i. Engineered: yes
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Organ: seed. Tissue: plasma.
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Biol. unit:
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Monomer (from PDB file)
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Resolution:
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Authors:
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A.Lombardi,G.De Simone,F.Nastri,S.Galdiero,R.Della Morte,N.Staiano, C.Pedone,M.Bolognesi,V.Pavone
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Key ref:
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A.Lombardi
et al.
(1999).
The crystal structure of alpha-thrombin-hirunorm IV complex reveals a novel specificity site recognition mode.
Protein Sci,
8,
91-95.
PubMed id:
DOI:
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Date:
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18-Sep-98
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Release date:
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15-Jun-99
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PROCHECK
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Headers
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References
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P00734
(THRB_HUMAN) -
Prothrombin from Homo sapiens
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Seq:
Struc:
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622 a.a.
36 a.a.
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Enzyme class:
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Chains L, H:
E.C.3.4.21.5
- thrombin.
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Reaction:
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Preferential cleavage: Arg-|-Gly; activates fibrinogen to fibrin and releases fibrinopeptide A and B.
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DOI no:
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Protein Sci
8:91-95
(1999)
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PubMed id:
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The crystal structure of alpha-thrombin-hirunorm IV complex reveals a novel specificity site recognition mode.
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A.Lombardi,
G.De Simone,
F.Nastri,
S.Galdiero,
R.Della Morte,
N.Staiano,
C.Pedone,
M.Bolognesi,
V.Pavone.
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ABSTRACT
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The X-ray crystal structure of the human alpha-thrombin-hirunorm IV complex has
been determined at 2.5 A resolution, and refined to an R-factor of 0.173. The
structure reveals an inhibitor binding mode distinctive of a true hirudin
mimetic, which justifies the high inhibitory potency and the selectivity of
hirunorm IV. This novel inhibitor, composed of 26 amino acids, interacts through
the N-terminal end with the alpha-thrombin active site in a nonsubstrate mode,
and binds specifically to the fibrinogen recognition exosite through the
C-terminal end. The backbone of the N-terminal tripeptide Chg1"-Arg2"-2Na13"
(Chg, cyclohexyl-glycine; 2Na1, beta-(2-naphthyl)-alanine) forms a parallel
beta-strand to the thrombin main-chain segment Ser214-Gly216. The Chg1" side
chain occupies the S2 site, Arg2" penetrates into the S1 specificity site, while
the 2Na13" side chain occupies the aryl binding site. The Arg2" side chain
enters the S1 specificity pocket from a position quite apart from the canonical
P1 site. This notwithstanding, the Arg2" side chain establishes the typical ion
pair with the carboxylate group of Asp189.
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Literature references that cite this PDB file's key reference
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PubMed id
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Reference
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J.J.Slon-Usakiewicz,
J.Sivaraman,
Y.Li,
M.Cygler,
and
Y.Konishi
(2000).
Design of P1' and P3' residues of trivalent thrombin inhibitors and their crystal structures.
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Biochemistry,
39,
2384-2391.
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PDB codes:
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A.Lombardi,
G.De Simone,
S.Galdiero,
N.Staiano,
F.Nastri,
and
V.Pavone
(1999).
From natural to synthetic multisite thrombin inhibitors.
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Biopolymers,
51,
19-39.
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The most recent references are shown first.
Citation data come partly from CiteXplore and partly
from an automated harvesting procedure. Note that this is likely to be
only a partial list as not all journals are covered by
either method. However, we are continually building up the citation data
so more and more references will be included with time.
Where a reference describes a PDB structure, the PDB
codes are
shown on the right.
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Links
