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PDBsum entry 1f0r
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protein ligands metals Protein-protein interface(s) links
Hydrolase PDB id
1f0r

 

 

 

 

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Contents
Protein chains
234 a.a. *
51 a.a. *
Ligands
815
Metals
_CA
Waters ×170
* Residue conservation analysis
PDB id:
1f0r
Name: Hydrolase
Title: Crystal structure of human coagulation factor xa complexed with rpr208815
Structure: Coagulation factor xa. Chain: a. Fragment: activated factor xa, heavy chain. Coagulation factor xa. Chain: b. Fragment: factor x light chain. Ec: 3.4.21.6
Source: Homo sapiens. Human. Organism_taxid: 9606. Organism_taxid: 9606
Biol. unit: Dimer (from PQS)
Resolution:
2.10Å     R-factor:   0.216     R-free:   0.263
Authors: S.Maignan,J.P.Guilloteau,S.Pouzieux,Y.M.Choi-Sledeski,M.R.Becker, S.I.Klein,W.R.Ewing,H.W.Pauls,A.P.Spada,V.Mikol
Key ref: S.Maignan et al. (2000). Crystal structures of human factor Xa complexed with potent inhibitors. J Med Chem, 43, 3226-3232. PubMed id: 10966741 DOI: 10.1021/jm000940u
Date:
17-May-00     Release date:   20-Sep-00    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P00742  (FA10_HUMAN) -  Coagulation factor X from Homo sapiens
Seq:
Struc: 		488 a.a.
234 a.a.
Protein chain
Pfam   ArchSchema ?
P00742  (FA10_HUMAN) -  Coagulation factor X from Homo sapiens
Seq:
Struc: 		488 a.a.
51 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: Chains A, B: E.C.3.4.21.6  - coagulation factor Xa.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Preferential cleavage: Arg-|-Thr and then Arg-|-Ile bonds in prothrombin to form thrombin.

 

 
DOI no: 10.1021/jm000940u J Med Chem 43:3226-3232 (2000)
PubMed id: 10966741  
 
 
Crystal structures of human factor Xa complexed with potent inhibitors.
S.Maignan, J.P.Guilloteau, S.Pouzieux, Y.M.Choi-Sledeski, M.R.Becker, S.I.Klein, W.R.Ewing, H.W.Pauls, A.P.Spada, V.Mikol.
 
  ABSTRACT  
 
Involved in the coagulation cascade, factor Xa (FXa) is a serine protease which has received great interest as a potential target for the development of new antithrombotics. Although there is a great wealth of structural data on thrombin complexes, few structures of ligand/FXa complexes have been reported, presumably because of the difficulty in growing crystals. Reproducible crystallization conditions for human des-Gla1-45 coagulation FXa have been found. This has led to an improvement in the diffraction quality of the crystals (about 2.1 A) when compared to the previously reported forms (2.3-2.8 A) thus providing a suitable platform for a structure-based drug design approach. A series of crystal structures of noncovalent inhibitors complexed with FXa have been determined, three of which are presented herein. These include compounds containing the benzamidine moiety and surrogates of the basic group. The benzamidine-containing compound binds in a canonical fashion typical of synthetic serine protease inhibitors. On the contrary, molecules that contain surrogates of the benzamidine group do not make direct hydrogen-bonding interactions with the carboxylate of Asp189 at the bottom of the S1 pocket. The structural data provide a likely explanation for the specificity of these inhibitors and a great aid in the design of bioavailable potent FXa inhibitors.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21328404 V.Hähnke, A.Klenner, F.Rippmann, and G.Schneider (2011).
Pharmacophore alignment search tool: Influence of the third dimension on text-based similarity searching.
  J Comput Chem, 32, 1618-1634.  
18615421 E.Luttmann, D.L.Ensign, V.Vaidyanathan, M.Houston, N.Rimon, J.Øland, G.Jayachandran, M.Friedrichs, and V.S.Pande (2009).
Accelerating molecular dynamic simulation on the cell processor and Playstation 3.
  J Comput Chem, 30, 268-274.  
19845314 H.Fan, J.J.Irwin, B.M.Webb, G.Klebe, B.K.Shoichet, and A.Sali (2009).
Molecular docking screens using comparative models of proteins.
  J Chem Inf Model, 49, 2512-2527.  
19186135 R.Chattopadhyay, R.Iacob, S.Sen, R.Majumder, K.B.Tomer, and B.R.Lentz (2009).
Functional and structural characterization of factor Xa dimer in solution.
  Biophys J, 96, 974-986.  
18941902 R.Gil-Redondo, J.Estrada, A.Morreale, F.Herranz, J.Sancho, and A.R.Ortiz (2009).
VSDMIP: virtual screening data management on an integrated platform.
  J Comput Aided Mol Des, 23, 171-184.  
19343764 Y.Tanrikulu, E.Proschak, T.Werner, T.Geppert, N.Todoroff, A.Klenner, T.Kottke, K.Sander, E.Schneider, R.Seifert, H.Stark, T.Clark, and G.Schneider (2009).
Homology model adjustment and ligand screening with a pseudoreceptor of the human histamine H4 receptor.
  ChemMedChem, 4, 820-827.  
17516427 E.Proschak, M.Rupp, S.Derksen, and G.Schneider (2008).
Shapelets: possibilities and limitations of shape-based virtual screening.
  J Comput Chem, 29, 108-114.  
18680100 N.Singh, and J.M.Briggs (2008).
Molecular dynamics simulations of Factor Xa: insight into conformational transition of its binding subsites.
  Biopolymers, 89, 1104-1113.  
18266362 R.Abel, T.Young, R.Farid, B.J.Berne, and R.A.Friesner (2008).
Role of the active-site solvent in the thermodynamics of factor Xa ligand binding.
  J Am Chem Soc, 130, 2817-2831.  
18077174 Y.Imaeda, T.Miyawaki, H.Sakamoto, F.Itoh, N.Konishi, K.Hiroe, M.Kawamura, T.Tanaka, and K.Kubo (2008).
Discovery of sulfonylalkylamides: A new class of orally active factor Xa inhibitors.
  Bioorg Med Chem, 16, 2243-2260.  
17191291 A.Di Fenza, A.Heine, U.Koert, and G.Klebe (2007).
Understanding Binding Selectivity toward Trypsin and Factor Xa: the Role of Aromatic Interactions.
  ChemMedChem, 2, 297-308.
PDB codes: 1y59 1y5a 1y5b 1y5u
17683371 J.T.Kohrt, C.F.Bigge, J.W.Bryant, A.Casimiro-Garcia, L.Chi, W.L.Cody, T.Dahring, D.A.Dudley, K.J.Filipski, S.Haarer, R.Heemstra, N.Janiczek, L.Narasimhan, T.McClanahan, J.T.Peterson, V.Sahasrabudhe, R.Schaum, C.A.Van Huis, K.M.Welch, E.Zhang, R.J.Leadley, and J.J.Edmunds (2007).
The discovery of (2R,4R)-N-(4-chlorophenyl)-N- (2-fluoro-4-(2-oxopyridin-1(2H)-yl)phenyl)-4-methoxypyrrolidine-1,2-dicarboxamide (PD 0348292), an orally efficacious factor Xa inhibitor.
  Chem Biol Drug Des, 70, 100-112.
PDB code: 2phb
17917295 T.Noguchi, N.Tanaka, T.Nishimata, R.Goto, M.Hayakawa, A.Sugidachi, T.Ogawa, F.Asai, and K.Fujimoto (2007).
Cinnamylindoline derivatives: synthesis and factor Xa (FXa) inhibitory activities.
  Chem Pharm Bull (Tokyo), 55, 1494-1504.  
16619025 D.J.Johnson, W.Li, T.E.Adams, and J.A.Huntington (2006).
Antithrombin-S195A factor Xa-heparin structure reveals the allosteric mechanism of antithrombin activation.
  EMBO J, 25, 2029-2037.
PDB code: 2gd4
16923021 K.M.Bromfield, N.S.Quinsey, P.J.Duggan, and R.N.Pike (2006).
Approaches to selective peptidic inhibitors of factor Xa.
  Chem Biol Drug Des, 68, 11-19.  
16477622 M.Nayal, and B.Honig (2006).
On the nature of cavities on protein surfaces: application to the identification of drug-binding sites.
  Proteins, 63, 892-906.  
16344948 S.Cotesta, and M.Stahl (2006).
The environment of amide groups in protein-ligand complexes: H-bonds and beyond.
  J Mol Model, 12, 436-444.  
15952226 K.Schärer, M.Morgenthaler, R.Paulini, U.Obst-Sander, D.W.Banner, D.Schlatter, J.Benz, M.Stihle, and F.Diederich (2005).
Quantification of cation-pi interactions in protein-ligand complexes: crystal-structure analysis of Factor Xa bound to a quaternary ammonium ion ligand.
  Angew Chem Int Ed Engl, 44, 4400-4404.
PDB code: 2bok
15044735 H.K.Leiros, B.O.Brandsdal, O.A.Andersen, V.Os, I.Leiros, R.Helland, J.Otlewski, N.P.Willassen, and A.O.Smalås (2004).
Trypsin specificity as elucidated by LIE calculations, X-ray structures, and association constant measurements.
  Protein Sci, 13, 1056-1070.
PDB codes: 1utj 1utk 1utl 1utm 1utn 1uto 1utp 1utq
12964191 C.Oostenbrink, and W.F.van Gunsteren (2003).
Single-step perturbations to calculate free energy differences from unphysical reference states: limits on size, flexibility, and character.
  J Comput Chem, 24, 1730-1739.  
12479872 J.P.Ludeman, R.N.Pike, K.M.Bromfield, P.J.Duggan, J.Cianci, B.Le Bonniec, J.C.Whisstock, and S.P.Bottomley (2003).
Determination of the P1', P2' and P3' subsite-specificity of factor Xa.
  Int J Biochem Cell Biol, 35, 221-225.  
12437122 D.Rauh, S.Reyda, G.Klebe, and M.T.Stubbs (2002).
Trypsin mutants for structure-based drug design: expression, refolding and crystallisation.
  Biol Chem, 383, 1309-1314.  
11854268 N.S.Quinsey, J.C.Whisstock, B.Le Bonniec, V.Louvain, S.P.Bottomley, and R.N.Pike (2002).
Molecular determinants of the mechanism underlying acceleration of the interaction between antithrombin and factor Xa by heparin pentasaccharide.
  J Biol Chem, 277, 15971-15978.  
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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