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PDBsum entry 2q9i
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Blood clotting
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PDB id
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2q9i
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Contents |
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67 a.a.
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303 a.a.
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292 a.a.
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54 a.a.
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* Residue conservation analysis
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PDB id:
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Blood clotting
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Title:
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Crystal structure of d-dimer from human fibrin complexed with met-his- arg-pro-tyr-amide.
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Structure:
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Fibrinogen alpha chain. Chain: a, d. Fragment: unp residues 130-216. Fibrinogen beta chain. Chain: b, e. Fragment: unp residues 164-491. Fibrinogen, gamma polypeptide. Chain: c, f. Fragment: unp residues 114-437.
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Synthetic: yes. Other_details: this sequence occurs naturally in humans.. Other_details: this sequence does not occur naturally.
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Resolution:
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2.80Å
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R-factor:
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0.216
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R-free:
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0.276
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Authors:
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R.F.Doolittle,L.Pandi
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Key ref:
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R.F.Doolittle
and
L.Pandi
(2007).
Probing the beta-chain hole of fibrinogen with synthetic peptides that differ at their amino termini.
Biochemistry,
46,
10033-10038.
PubMed id:
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Date:
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12-Jun-07
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Release date:
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11-Dec-07
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PROCHECK
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Headers
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References
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P02671
(FIBA_HUMAN) -
Fibrinogen alpha chain from Homo sapiens
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Seq:
Struc:
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866 a.a.
67 a.a.
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P02675
(FIBB_HUMAN) -
Fibrinogen beta chain from Homo sapiens
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Seq:
Struc:
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491 a.a.
303 a.a.
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Biochemistry
46:10033-10038
(2007)
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PubMed id:
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Probing the beta-chain hole of fibrinogen with synthetic peptides that differ at their amino termini.
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R.F.Doolittle,
L.Pandi.
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ABSTRACT
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In a recent report, we showed that alanine can replace glycine at the amino
terminus of synthetic B-knobs that bind to human fibrin(ogen). We now report a
survey of 13 synthetic peptides with the general sequence XHRPYam, all tested
with regard to their ability to delay fibrinolysis in an in vitro system
activated by t-PA, the results being used as measures of binding affinity to the
betaC hole. Unexpectedly, some large and bulky amino acids, including methionine
and arginine, are effective binders. Amino acids that branch at the beta carbon
(valine, isoleucine, and threonine) do not bind effectively. Crystal structures
were determined for two of the peptides (GHRPYam and MHRPYam) complexed with
fibrin fragment D-dimer; the modeling of various other side chains showed
clashing in the cases of beta-carbon substituents. The two crystal structures
also showed that the enhanced binding observed with pentapeptides with
carboxyl-terminal tyrosine, compared with that of their tetrapeptide
equivalents, is attributable to an interaction between the tyrosine side chain
and a guanidino group of a nearby arginine (beta406). The equivalent position in
gamma-chains of human fibrin(ogen) is occupied by a lysine (gamma338), but in
chicken and lamprey fibrin(ogen), it is an arginine, just as occurs in beta
chains. Accordingly, the peptides GPRPam and GPRPYam, which are surrogate
A-knobs, were tested for their influence on fibrin polymerization with
fibrinogen from lamprey and humans. In lampreys, GPRPYam is a significantly
better inhibitor, but in humans, it is less effective than GPRPam, indicating
that in the lamprey system the same tyrosine-arginine interaction can also occur
in the gamma-chain setting.
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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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S.E.Stabenfeldt,
J.J.Gossett,
and
T.H.Barker
(2010).
Building better fibrin knob mimics: an investigation of synthetic fibrin knob peptide structures in solution and their dynamic binding with fibrinogen/fibrin holes.
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Blood,
116,
1352-1359.
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R.A.Campbell,
K.A.Overmyer,
C.H.Selzman,
B.C.Sheridan,
and
A.S.Wolberg
(2009).
Contributions of extravascular and intravascular cells to fibrin network formation, structure, and stability.
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Blood,
114,
4886-4896.
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S.R.Bowley,
and
S.T.Lord
(2009).
Fibrinogen variant BbetaD432A has normal polymerization but does not bind knob "B".
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Blood,
113,
4425-4430.
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PDB code:
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S.S.Adam,
N.S.Key,
and
C.S.Greenberg
(2009).
D-dimer antigen: current concepts and future prospects.
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Blood,
113,
2878-2887.
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W.G.Kerrick,
K.Kazmierczak,
Y.Xu,
Y.Wang,
and
D.Szczesna-Cordary
(2009).
Malignant familial hypertrophic cardiomyopathy D166V mutation in the ventricular myosin regulatory light chain causes profound effects in skinned and intact papillary muscle fibers from transgenic mice.
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FASEB J,
23,
855-865.
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J.W.Weisel
(2007).
Which knobs fit into which holes in fibrin polymerization?
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J Thromb Haemost,
5,
2340-2343.
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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
code is
shown on the right.
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