spacer
spacer

PDBsum entry 1e04

Go to PDB code: 
protein ligands Protein-protein interface(s) links
Blood clotting PDB id
1e04
Jmol
Contents
Protein chain
403 a.a. *
Ligands
NAG-NAG ×4
MAN
NAG-NAG-BMA
GOL ×2
NAG-NAG-BMA-MAN-
MAN
PO4
Waters ×84
* Residue conservation analysis
PDB id:
1e04
Name: Blood clotting
Title: Plasma beta antithrombin-iii
Structure: Antithrombin-iii. Chain: i, l
Source: Homo sapiens. Human. Organism_taxid: 9606. Other_details: plasma beta antithrombin-iii
Biol. unit: Monomer (from PDB file)
Resolution:
2.60Å     R-factor:   0.205     R-free:   0.243
Authors: A.J.Mccoy,R.Skinner,J.-P.Abrahams,X.Y.Pei,R.W.Carrell
Key ref: A.J.McCoy et al. (2003). Structure of beta-antithrombin and the effect of glycosylation on antithrombin's heparin affinity and activity. J Mol Biol, 326, 823-833. PubMed id: 12581643
Date:
09-Mar-00     Release date:   02-Jun-00    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P01008  (ANT3_HUMAN) -  Antithrombin-III
Seq:
Struc:
464 a.a.
403 a.a.
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     extracellular region   5 terms 
  Biological process     regulation of blood coagulation, intrinsic pathway   8 terms 
  Biochemical function     protein binding     5 terms  

 

 
J Mol Biol 326:823-833 (2003)
PubMed id: 12581643  
 
 
Structure of beta-antithrombin and the effect of glycosylation on antithrombin's heparin affinity and activity.
A.J.McCoy, X.Y.Pei, R.Skinner, J.P.Abrahams, R.W.Carrell.
 
  ABSTRACT  
 
Antithrombin is a member of the serpin family of protease inhibitors and the major inhibitor of the blood coagulation cascade. It is unique amongst the serpins in that it circulates in a conformation that is inactive against its target proteases. Activation of antithrombin is brought about by a conformational change initiated upon binding heparin or heparan sulphate. Two isoforms exist in the circulation, alpha-antithrombin and beta-antithrombin, which differ in the amount of glycosylation present on the polypeptide chain; beta-antithrombin lacks the carbohydrate present at Asn135 in alpha-antithrombin. Of the two forms, beta-antithrombin has the higher affinity for heparin and thus functions as the major inhibitor in vivo even though it is the less abundant form. The reason for the differences in heparin affinity between the alpha and beta-forms have been shown to be due to the additional carbohydrate changing the rate of the conformational change. Here, we describe the most accurate structures of alpha-antithrombin and alpha-antithrombin+heparin pentasaccharide reported to date (2.6A and 2.9A resolution, respectively, both re-refinements using old data), and the structure of beta-antithrombin (2.6A resolution). The new structures have a remarkable degree of ordered carbohydrate and include parts of the antithrombin chain not modeled before. The structures have allowed a detailed comparison of the conformational differences between the three. They show that the structural basis of the lower affinity for heparin of alpha-antithrombin over beta-antithrombin is due to the conformational change that occurs upon heparin binding being sterically hindered by the presence of the additional bulky carbohydrate at Asn135.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
  21465556 C.An, S.Lovell, M.R.Kanost, K.P.Battaile, and K.Michel (2011).
Crystal structure of native Anopheles gambiae serpin-2, a negative regulator of melanization in mosquitoes.
  Proteins, 79, 1999-2003.
PDB code: 3pzf
  20435622 I.Martínez-Martínez, A.Ordóñez, J.Navarro-Fernández, A.Pérez-Lara, R.Gutiérrez-Gallego, R.Giraldo, C.Martínez, E.Llop, V.Vicente, and J.Corral (2010).
Antithrombin Murcia (K241E) causing antithrombin deficiency: a possible role for altered glycosylation.
  Haematologica, 95, 1358-1365.  
  19712578 Y.Chen, W.Tan, S.Qin, J.Zhang, H.Bu, Y.Li, Y.Lu, and J.Cheng (2009).
Cloning of the full-length cDNA of porcine antithrombin III and comparison with its human homolog.
  Comp Med, 59, 372-377.  
18512669 S.Amon, A.D.Zamfir, and A.Rizzi (2008).
Glycosylation analysis of glycoproteins and proteoglycans using capillary electrophoresis-mass spectrometry strategies.
  Electrophoresis, 29, 2485-2507.  
17385667 E.Seyrek, P.L.Dubin, and J.Henriksen (2007).
Nonspecific electrostatic binding characteristics of the heparin-antithrombin interaction.
  Biopolymers, 86, 249-259.  
17635716 J.C.Rau, L.M.Beaulieu, J.A.Huntington, and F.C.Church (2007).
Serpins in thrombosis, hemostasis and fibrinolysis.
  J Thromb Haemost, 5, 102-115.  
17644521 M.A.Klieber, C.Underhill, G.L.Hammond, and Y.A.Muller (2007).
Corticosteroid-binding globulin, a structural basis for steroid transport and proteinase-triggered release.
  J Biol Chem, 282, 29594-29603.
PDB codes: 2v6d 2v95
16973611 D.J.Johnson, J.Langdown, W.Li, S.A.Luis, T.P.Baglin, and J.A.Huntington (2006).
Crystal structure of monomeric native antithrombin reveals a novel reactive center loop conformation.
  J Biol Chem, 281, 35478-35486.
PDB codes: 1t1f 2b5t 2beh
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
16820297 J.A.Huntington (2006).
Shape-shifting serpins--advantages of a mobile mechanism.
  Trends Biochem Sci, 31, 427-435.  
16145710 A.Plematl, U.M.Demelbauer, D.Josic, and A.Rizzi (2005).
Determination of the site-specific and isoform-specific glycosylation in human plasma-derived antithrombin by IEF and capillary HPLC-ESI-MS/MS.
  Proteomics, 5, 4025-4033.  
14623882 D.J.Johnson, and J.A.Huntington (2004).
The influence of hinge region residue Glu-381 on antithrombin allostery and metastability.
  J Biol Chem, 279, 4913-4921.
PDB code: 1oyh
14705167 U.R.Desai (2004).
New antithrombin-based anticoagulants.
  Med Res Rev, 24, 151-181.  
14532267 G.Izaguirre, W.Zhang, R.Swanson, T.Bedsted, and S.T.Olson (2003).
Localization of an antithrombin exosite that promotes rapid inhibition of factors Xa and IXa dependent on heparin activation of the serpin.
  J Biol Chem, 278, 51433-51440.  
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.