PDBsum entry 1huw

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Hormone PDB id
Protein chain
166 a.a. *
Waters ×77
* Residue conservation analysis
PDB id:
Name: Hormone
Title: The crystal structure of affinity-matured human growth hormone at 2 angstroms resolution
Structure: Human growth hormone. Chain: a. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606
Biol. unit: Dimer (from PQS)
2.00Å     R-factor:   0.185    
Authors: M.H.Ultsch,W.S.Somers,A.A.Kossiakoff,A.M.De Vos
Key ref: M.H.Ultsch et al. (1994). The crystal structure of affinity-matured human growth hormone at 2 A resolution. J Mol Biol, 236, 286-299. PubMed id: 8107110
22-Sep-93     Release date:   31-Jan-94    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P01241  (SOMA_HUMAN) -  Somatotropin
217 a.a.
166 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 15 residue positions (black crosses)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     extracellular region   2 terms 
  Biological process     bone maturation   16 terms 
  Biochemical function     protein binding     6 terms  


J Mol Biol 236:286-299 (1994)
PubMed id: 8107110  
The crystal structure of affinity-matured human growth hormone at 2 A resolution.
M.H.Ultsch, W.Somers, A.A.Kossiakoff, Vos.
A variant of human growth hormone (hGH), in which 15 mutations were introduced with phage display mutagenesis to improve receptor binding affinity by 400-fold, yielded two related crystal forms diffracting to high resolution. The structure of this variant was determined in both crystal forms, one at 2.0 A resolution and one at 2.4 A resolution, using molecular replacement with wild-type hGH taken from the receptor complex structure as a search model. Crystallographic refinement of the 2 A structure gave an R-value R-value of 18.5% for data in the resolution range 8 to 2 A. The final model consists of residues 1 to 128 and 155 to 191, with three side-chains modeled in alternative conformations, together with 77 water molecules. Comparison of the structure with wild-type hGH shows that most of the secondary structural elements are unchanged. The exception is the first turn of the third helix in the four-helix bundle core, which is unraveled in the present variant. Analysis of the two related packing environments suggests that this change is caused by crystal packing forces. A large change in the orientation of a short segment of helix found in the connection between the first two core helices is interpreted as evidence for rigid-body variability of this helical segment. Analysis of the mutations in light of the structure of the wild-type hGH/receptor complex shows that six of the mutations are buried in the hormone, whereas the remaining nine involve residues that interact with the receptor in the complex.

Literature references that cite this PDB file's key reference

  PubMed id Reference
17916398 A.Fontana, B.Spolaore, A.Mero, and F.M.Veronese (2008).
Site-specific modification and PEGylation of pharmaceutical proteins mediated by transglutaminase.
  Adv Drug Deliv Rev, 60, 13-28.  
18407771 F.Roelfsema, N.R.Biermasz, A.M.Pereira, and J.A.Romijn (2008).
The role of pegvisomant in the treatment of acromegaly.
  Expert Opin Biol Ther, 8, 691-704.  
17705152 S.B.Joshi, T.J.Kamerzell, C.McNown, and C.R.Middaugh (2008).
The interaction of heparin/polyanions with bovine, porcine, and human growth hormone.
  J Pharm Sci, 97, 1368-1385.  
17927666 K.Kannenberg, N.E.Wittekindt, S.Tippmann, H.Wolburg, M.B.Ranke, and G.Binder (2007).
Mutant and misfolded human growth hormone is rapidly degraded through the proteasomal degradation pathway in a cellular model for isolated growth hormone deficiency type II.
  J Neuroendocrinol, 19, 882-890.  
17722273 F.Roelfsema, N.R.Biermasz, A.M.Pereira, and J.Romijn (2006).
Nanomedicines in the treatment of acromegaly: focus on pegvisomant.
  Int J Nanomedicine, 1, 385-398.  
16269515 J.F.Langenheim, D.Tan, A.M.Walker, and W.Y.Chen (2006).
Two wrongs can make a right: dimers of prolactin and growth hormone receptor antagonists behave as agonists.
  Mol Endocrinol, 20, 661-674.  
16180132 E.N.Lee, Y.M.Kim, H.J.Lee, S.W.Park, H.Y.Jung, J.M.Lee, Y.H.Ahn, and J.Kim (2005).
Stabilizing peptide fusion for solving the stability and solubility problems of therapeutic proteins.
  Pharm Res, 22, 1735-1746.  
15857837 J.L.Kouadio, J.R.Horn, G.Pal, and A.A.Kossiakoff (2005).
Shotgun alanine scanning shows that growth hormone can bind productively to its receptor through a drastically minimized interface.
  J Biol Chem, 280, 25524-25532.  
12682073 K.M.Duda, and C.L.Brooks (2003).
Identification of residues outside the two binding sites that are critical for activation of the lactogenic activity of human growth hormone.
  J Biol Chem, 278, 22734-22739.  
11750880 A.E.Geddis, H.M.Linden, and K.Kaushansky (2002).
Thrombopoietin: a pan-hematopoietic cytokine.
  Cytokine Growth Factor Rev, 13, 61-73.  
11591710 R.J.St John, J.F.Carpenter, C.Balny, and T.W.Randolph (2001).
High pressure refolding of recombinant human growth hormone from insoluble aggregates. Structural transformations, kinetic barriers, and energetics.
  J Biol Chem, 276, 46856-46863.  
11015692 T.H.Yang, J.L.Cleland, X.Lam, J.D.Meyer, L.S.Jones, T.W.Randolph, M.C.Manning, and J.F.Carpenter (2000).
Effect of zinc binding and precipitation on structures of recombinant human growth hormone and nerve growth factor.
  J Pharm Sci, 89, 1480-1485.  
10494829 J.Grötzinger, T.Kernebeck, K.J.Kallen, and S.Rose-John (1999).
IL-6 type cytokine receptor complexes: hexamer, tetramer or both?
  Biol Chem, 380, 803-813.  
10557267 R.J.St John, J.F.Carpenter, and T.W.Randolph (1999).
High pressure fosters protein refolding from aggregates at high concentrations.
  Proc Natl Acad Sci U S A, 96, 13029-13033.  
  9655339 I.Gomez-Orellana, B.Variano, J.Miura-Fraboni, S.Milstein, and D.R.Paton (1998).
Thermodynamic characterization of an intermediate state of human growth hormone.
  Protein Sci, 7, 1352-1358.  
10189266 N.B.Bam, J.L.Cleland, J.Yang, M.C.Manning, J.F.Carpenter, R.F.Kelley, and T.W.Randolph (1998).
Tween protects recombinant human growth hormone against agitation-induced damage via hydrophobic interactions.
  J Pharm Sci, 87, 1554-1559.  
9241412 B.A.Katz (1997).
Structural and mechanistic determinants of affinity and specificity of ligands discovered or engineered by phage display.
  Annu Rev Biophys Biomol Struct, 26, 27-45.  
9278420 B.K.Klein, Y.Feng, C.A.McWherter, W.F.Hood, K.Paik, and J.P.McKearn (1997).
The receptor binding site of human interleukin-3 defined by mutagenesis and molecular modeling.
  J Biol Chem, 272, 22630-22641.  
9254611 D.H.Purvis, and B.C.Mabbutt (1997).
Solution dynamics and secondary structure of murine leukemia inhibitory factor: a four-helix cytokine with a rigid CD loop.
  Biochemistry, 36, 10146-10154.  
9261160 F.C.Peterson, and C.L.Brooks (1997).
Identification of a motif associated with the lactogenic actions of human growth hormone.
  J Biol Chem, 272, 21444-21448.  
  9144766 R.J.Simpson, A.Hammacher, D.K.Smith, J.M.Matthews, and L.D.Ward (1997).
Interleukin-6: structure-function relationships.
  Protein Sci, 6, 929-955.  
8874031 S.Kumar, and M.Bansal (1996).
Structural and sequence characteristics of long alpha helices in globular proteins.
  Biophys J, 71, 1574-1586.  
  7744001 G.Paonessa, R.Graziani, A.De Serio, R.Savino, L.Ciapponi, A.Lahm, A.L.Salvati, C.Toniatti, and G.Ciliberto (1995).
Two distinct and independent sites on IL-6 trigger gp 130 dimer formation and signalling.
  EMBO J, 14, 1942-1951.  
7773741 H.R.Mott, and I.D.Campbell (1995).
Four-helix bundle growth factors and their receptors: protein-protein interactions.
  Curr Opin Struct Biol, 5, 114-121.  
  7796798 N.Q.McDonald, N.Panayotatos, and W.A.Hendrickson (1995).
Crystal structure of dimeric human ciliary neurotrophic factor determined by MAD phasing.
  EMBO J, 14, 2689-2699.
PDB code: 1cnt
  7849586 A.A.Kossiakoff, W.Somers, M.Ultsch, K.Andow, Y.A.Muller, and A.M.De Vos (1994).
Comparison of the intermediate complexes of human growth hormone bound to the human growth hormone and prolactin receptors.
  Protein Sci, 3, 1697-1705.  
7529123 P.Bamborough, C.J.Hedgecock, and W.G.Richards (1994).
The interleukin-2 and interleukin-4 receptors studied by molecular modelling.
  Structure, 2, 839-851.
PDB codes: 1ill 1ilm 1iln
7764900 T.Clackson, and J.A.Wells (1994).
In vitro selection from protein and peptide libraries.
  Trends Biotechnol, 12, 173-184.  
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.