PDBsum entry 1hfz

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Glycoprotein PDB id
Protein chains
123 a.a. *
_CA ×4
Waters ×60
* Residue conservation analysis
PDB id:
Name: Glycoprotein
Title: Alpha-lactalbumin
Structure: Alpha-lactalbumin. Chain: a, b, c, d. Engineered: yes. Mutation: yes
Source: Bos taurus. Cattle. Organism_taxid: 9913. Gene: bovine alpha-lactalbumin cdna. Expressed in: escherichia coli. Expression_system_taxid: 562. Other_details: t7 RNA polymerase
2.30Å     R-factor:   0.208     R-free:   0.303
Authors: A.C.W.Pike,K.Brew,K.R.Acharya
Key ref:
A.C.Pike et al. (1996). Crystal structures of guinea-pig, goat and bovine alpha-lactalbumin highlight the enhanced conformational flexibility of regions that are significant for its action in lactose synthase. Structure, 4, 691-703. PubMed id: 8805552 DOI: 10.1016/S0969-2126(96)00075-5
13-Jun-96     Release date:   29-Jul-97    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
P00711  (LALBA_BOVIN) -  Alpha-lactalbumin
142 a.a.
123 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 2 residue positions (black crosses)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     extracellular region   1 term 
  Biological process     lactose biosynthetic process   1 term 
  Biochemical function     identical protein binding     4 terms  


DOI no: 10.1016/S0969-2126(96)00075-5 Structure 4:691-703 (1996)
PubMed id: 8805552  
Crystal structures of guinea-pig, goat and bovine alpha-lactalbumin highlight the enhanced conformational flexibility of regions that are significant for its action in lactose synthase.
A.C.Pike, K.Brew, K.R.Acharya.
BACKGROUND: The regulation of milk lactose biosynthesis is highly dependent on the action of a specifier protein, alpha-lactalbumin (LA). Together with a glycosyltransferase, LA forms the enzyme complex lactose synthase. LA promotes the binding of glucose to the complex and facilitates the biosynthesis of lactose. To gain further insight into the molecular basis of LA function in lactose synthase we have determined the structures of three species variants of LA. RESULTS: The crystal structures of guinea-pig, goat and a recombinant from of bovine LA have been determined using molecular replacement techniques. Overall, the structures are very similar and reflect their high degree of amino acid sequence identity (66-94%). Nonetheless, the structures show that a portion of the molecule (residues 105-110), known to be important for function, exhibits a variety of distinct conformers. This region lies adjacent to two residues (Phe31 and His32) that have been implicated in monosaccharide binding by lactose synthase and its conformation has significant effects on the environments of these functional groups. The crystal structures also demonstrate that residues currently implicated in LA's modulatory properties are located in a region of the structure that has relatively high thermal parameters and is therefore probably flexible in vivo. CONCLUSIONS: LA's proposed interaction site for the catalytic component of the lactose synthase complex is primarily located in the flexible C-terminal portion of the molecule. This general observation implies that conformational adjustments may be important for the formation and function of lactose synthase.
  Selected figure(s)  
Figure 4.
Figure 4. Conformation of residues 105–110. Stereoviews of the region encompassing residues 105–110 are shown schematically for (a) mLA, (b) GOLA and (c) GPLA. All three molecules are viewed in the same orientation. (Figure produced using MOLSCRIPT [60]). Figure 4. Conformation of residues 105–110. Stereoviews of the region encompassing residues 105–110 are shown schematically for (a) mLA, (b) GOLA and (c) GPLA. All three molecules are viewed in the same orientation. (Figure produced using MOLSCRIPT [[5]60]).
Figure 5.
Figure 5. Aromatic cluster I superposition. The relative orientations of the side chains in aromatic cluster I are shown for HLA (blue), mLA (red), GPLA (green) and GOLA (yellow). The flexible loop region (upper right) and the position of Leu110 are also shown. (Figure produced using MOLSCRIPT [60]). Figure 5. Aromatic cluster I superposition. The relative orientations of the side chains in aromatic cluster I are shown for HLA (blue), mLA (red), GPLA (green) and GOLA (yellow). The flexible loop region (upper right) and the position of Leu110 are also shown. (Figure produced using MOLSCRIPT [[3]60]).
  The above figures are reprinted by permission from Cell Press: Structure (1996, 4, 691-703) copyright 1996.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
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How useful is ion mobility mass spectrometry for structural biology? The relationship between protein crystal structures and their collision cross sections in the gas phase.
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Application of molecular replacement to protein powder data from image plates.
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16791499 H.Van Dael, and A.Chedad (2006).
An equilibrium and a kinetic stopped-flow fluorescence study of the binding of various metal ions to goat alpha-lactalbumin.
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16731974 J.Wirmer, H.Berk, R.Ugolini, C.Redfield, and H.Schwalbe (2006).
Characterization of the unfolded state of bovine alpha-lactalbumin and comparison with unfolded states of homologous proteins.
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16823898 P.Schanda, V.Forge, and B.Brutscher (2006).
HET-SOFAST NMR for fast detection of structural compactness and heterogeneity along polypeptide chains.
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15861407 A.Vanhooren, A.Chedad, V.Farkas, Z.Majer, M.Joniau, H.Van Dael, and I.Hanssens (2005).
Tryptophan to phenylalanine substitutions allow differentiation of short- and long-range conformational changes during denaturation of goat alpha-lactalbumin.
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15576567 F.A.Chowdhury, and D.P.Raleigh (2005).
A comparative study of the alpha-subdomains of bovine and human alpha-lactalbumin reveals key differences that correlate with molten globule stability.
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16121399 M.Mizuguchi, A.Matsuura, Y.Nabeshima, K.Masaki, M.Watanabe, T.Aizawa, M.Demura, K.Nitta, Y.Mori, H.Shinoda, and K.Kawano (2005).
Effects of the stabilization of the molten globule state on the folding mechanism of alpha-lactalbumin: a study of a chimera of bovine and human alpha-lactalbumin.
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15853802 Laureto, E.Frare, F.Battaglia, M.F.Mossuto, V.N.Uversky, and A.Fontana (2005).
Protein dissection enhances the amyloidogenic properties of alpha-lactalbumin.
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15340922 A.Chedad, and H.Van Dael (2004).
Kinetics of folding and unfolding of goat alpha-lactalbumin.
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15268505 Vries (2004).
Monte Carlo simulations of flexible polyanions complexing with whey proteins at their isoelectric point.
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12660251 A.V.Agasøster, ..Halskau, E.Fuglebakk, N.A.Frøystein, A.Muga, H.Holmsen, and A.Martínez (2003).
The interaction of peripheral proteins and membranes studied with alpha-lactalbumin and phospholipid bilayers of various compositions.
  J Biol Chem, 278, 21790-21797.  
12784209 E.A.Permyakov, S.E.Permyakov, G.Y.Deikus, L.A.Morozova-Roche, V.M.Grishchenko, L.P.Kalinichenko, and V.N.Uversky (2003).
Ultraviolet illumination-induced reduction of alpha-lactalbumin disulfide bridges.
  Proteins, 51, 498-503.  
11751327 A.Vanhooren, K.Vanhee, K.Noyelle, Z.Majer, M.Joniau, and I.Hanssens (2002).
Structural basis for difference in heat capacity increments for Ca(2+) binding to two alpha-lactalbumins.
  Biophys J, 82, 407-417.  
11782453 M.F.Engel, C.P.van Mierlo, and A.J.Visser (2002).
Kinetic and structural characterization of adsorption-induced unfolding of bovine alpha -lactalbumin.
  J Biol Chem, 277, 10922-10930.  
12211019 M.Mizuguchi, Y.Kobashigawa, Y.Kumaki, M.Demura, K.Kawano, and K.Nitta (2002).
Effects of a helix substitution on the folding mechanism of bovine alpha-lactalbumin.
  Proteins, 49, 95.  
12021434 P.O.Craig, D.B.Ureta, and J.M.Delfino (2002).
Probing protein conformation with a minimal photochemical reagent.
  Protein Sci, 11, 1353-1366.  
12360528 P.Polverino de Laureto, E.Frare, R.Gottardo, and A.Fontana (2002).
Molten globule of bovine alpha-lactalbumin at neutral pH induced by heat, trifluoroethanol, and oleic acid: a comparative analysis by circular dichroism spectroscopy and limited proteolysis.
  Proteins, 49, 385-397.  
12441391 P.Polverino de Laureto, E.Frare, R.Gottardo, H.Van Dael, and A.Fontana (2002).
Partly folded states of members of the lysozyme/lactalbumin superfamily: a comparative study by circular dichroism spectroscopy and limited proteolysis.
  Protein Sci, 11, 2932-2946.  
11536356 K.Horii, M.Saito, T.Yoda, K.Tsumoto, M.Matsushima, K.Kuwajima, and I.Kumagai (2001).
Contribution of Thr29 to the thermodynamic stability of goat alpha-lactalbumin as determined by experimental and theoretical approaches.
  Proteins, 45, 16-29.
PDB codes: 1fkq 1fkv
11488928 P.Polverino de Laureto, D.Vinante, E.Scaramella, E.Frare, and A.Fontana (2001).
Stepwise proteolytic removal of the beta subdomain in alpha-lactalbumin. The protein remains folded and can form the molten globule in acid solution.
  Eur J Biochem, 268, 4324-4333.  
11093260 T.Yoda, M.Saito, M.Arai, K.Horii, K.Tsumoto, M.Matsushima, I.Kumagai, and K.Kuwajima (2001).
Folding-unfolding of goat alpha-lactalbumin studied by stopped-flow circular dichroism and molecular dynamics simulations.
  Proteins, 42, 49-65.  
11135190 W.Dzwolak, M.Kato, A.Shimizu, and Y.Taniguchi (2001).
FTIR study on heat-induced and pressure-assisted cold-induced changes in structure of bovine alpha-lactalbumin: stabilizing role of calcium ion.
  Biopolymers, 62, 29-39.  
10861388 E.W.Blanch, L.A.Morozova-Roche, L.Hecht, W.Noppe, and L.D.Barron (2000).
Raman optical activity characterization of native and molten globule states of equine lysozyme: comparison with hen lysozyme and bovine alpha-lactalbumin.
  Biopolymers, 57, 235-248.  
10813835 S.E.Permyakov, D.B.Veprintsev, C.L.Brooks, E.A.Permyakov, and L.J.Berliner (2000).
Zinc binding in bovine alpha-lactalbumin: sequence homology may not be a predictor of subtle functional features.
  Proteins, 40, 106-111.  
11112553 T.K.Chaudhuri, M.Arai, T.P.Terada, T.Ikura, and K.Kuwajima (2000).
Equilibrium and kinetic studies on folding of the authentic and recombinant forms of human alpha-lactalbumin by circular dichroism spectroscopy.
  Biochemistry, 39, 15643-15651.  
10727216 T.Koshiba, M.Yao, Y.Kobashigawa, M.Demura, A.Nakagawa, I.Tanaka, K.Kuwajima, and K.Nitta (2000).
Structure and thermodynamics of the extraordinarily stable molten globule state of canine milk lysozyme.
  Biochemistry, 39, 3248-3257.
PDB code: 1qqy
10451551 D.B.Veprintsev, M.Narayan, S.E.Permyakov, V.N.Uversky, C.L.Brooks, A.M.Cherskaya, E.A.Permyakov, and L.J.Berliner (1999).
Fine tuning the N-terminus of a calcium binding protein: alpha-lactalbumin.
  Proteins, 37, 65-72.  
10561612 K.Takano, K.Tsuchimori, Y.Yamagata, and K.Yutani (1999).
Effect of foreign N-terminal residues on the conformational stability of human lysozyme.
  Eur J Biochem, 266, 675-682.
PDB codes: 1c43 1c45 1c46
10393171 L.N.Gastinel, C.Cambillau, and Y.Bourne (1999).
Crystal structures of the bovine beta4galactosyltransferase catalytic domain and its complex with uridine diphosphogalactose.
  EMBO J, 18, 3546-3557.
PDB codes: 1fgx 1fr8
  10595532 P.Polverino de Laureto, E.Scaramella, M.Frigo, F.G.Wondrich, V.De Filippis, M.Zambonin, and A.Fontana (1999).
Limited proteolysis of bovine alpha-lactalbumin: isolation and characterization of protein domains.
  Protein Sci, 8, 2290-2303.  
  10338020 P.R.D'Silva, and A.K.Lala (1999).
Hydrophobic photolabeling as a new method for structural characterization of molten globule and related protein folding intermediates.
  Protein Sci, 8, 1099-1103.  
10446358 W.Dzwolak, M.Kato, A.Shimizu, and Y.Taniguchi (1999).
Fourier-transform infrared spectroscopy study of the pressure-induced changes in the structure of the bovine alpha-lactalbumin: the stabilizing role of the calcium ion.
  Biochim Biophys Acta, 1433, 45-55.  
  9761482 K.Gast, D.Zirwer, M.Müller-Frohne, and G.Damaschun (1998).
Compactness of the kinetic molten globule of bovine alpha-lactalbumin: a dynamic light scattering study.
  Protein Sci, 7, 2004-2011.  
  9684889 M.Ikeguchi, M.Fujino, M.Kato, K.Kuwajima, and S.Sugai (1998).
Transition state in the folding of alpha-lactalbumin probed by the 6-120 disulfide bond.
  Protein Sci, 7, 1564-1574.  
  9792102 M.Kikuchi, K.Kawano, and K.Nitta (1998).
Calcium-binding and structural stability of echidna and canine milk lysozymes.
  Protein Sci, 7, 2150-2155.  
9537992 N.Chandra, K.Brew, and K.R.Acharya (1998).
Structural evidence for the presence of a secondary calcium binding site in human alpha-lactalbumin.
  Biochemistry, 37, 4767-4772.
PDB code: 1a4v
  9761473 S.Kim, and J.Baum (1998).
Electrostatic interactions in the acid denaturation of alpha-lactalbumin determined by NMR.
  Protein Sci, 7, 1930-1938.  
9109670 B.Kuhlman, J.A.Boice, W.J.Wu, R.Fairman, and D.P.Raleigh (1997).
Calcium binding peptides from alpha-lactalbumin: implications for protein folding and stability.
  Biochemistry, 36, 4607-4615.  
9431992 M.Mizuguchi, M.Nara, Y.Ke, K.Kawano, T.Hiraoki, and K.Nitta (1997).
Fourier-transform infrared spectroscopic studies on the coordination of the side-chain COO- groups to Ca2+ in equine lysozyme.
  Eur J Biochem, 250, 72-76.  
9305954 P.J.Anderson, C.L.Brooks, and L.J.Berliner (1997).
Functional identification of calcium binding residues in bovine alpha-lactalbumin.
  Biochemistry, 36, 11648-11654.  
  9307874 P.K.Qasba, and S.Kumar (1997).
Molecular divergence of lysozymes and alpha-lactalbumin.
  Crit Rev Biochem Mol Biol, 32, 255-306.  
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