PDBsum entry 1hny

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Hydrolase (o-glycosyl) PDB id
Protein chain
496 a.a. *
Waters ×359
* Residue conservation analysis
PDB id:
Name: Hydrolase (o-glycosyl)
Title: The structure of human pancreatic alpha-amylase at 1.8 angstroms resolution and comparisons with related enzymes
Structure: Human pancreatic alpha-amylase. Chain: a. Ec:
Source: Homo sapiens. Human. Organism_taxid: 9606. Organ: pancreas
1.80Å     R-factor:   0.174    
Authors: Y.Luo,G.D.Brayer
Key ref:
G.D.Brayer et al. (1995). The structure of human pancreatic alpha-amylase at 1.8 A resolution and comparisons with related enzymes. Protein Sci, 4, 1730-1742. PubMed id: 8528071 DOI: 10.1002/pro.5560040908
28-Jun-95     Release date:   08-Mar-96    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P04746  (AMYP_HUMAN) -  Pancreatic alpha-amylase
511 a.a.
496 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Enzyme reactions 
   Enzyme class: E.C.  - Alpha-amylase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Endohydrolysis of 1,4-alpha-glucosidic linkages in oligosaccharides and polysaccharides.
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     extracellular region   3 terms 
  Biological process     metabolic process   5 terms 
  Biochemical function     catalytic activity     8 terms  


DOI no: 10.1002/pro.5560040908 Protein Sci 4:1730-1742 (1995)
PubMed id: 8528071  
The structure of human pancreatic alpha-amylase at 1.8 A resolution and comparisons with related enzymes.
G.D.Brayer, Y.Luo, S.G.Withers.
The structure of human pancreatic alpha-amylase has been determined to 1.8 A resolution using X-ray diffraction techniques. This enzyme is found to be composed of three structural domains. The largest is Domain A (residues 1-99, 169-404), which forms a central eight-stranded parallel beta-barrel, to one end of which are located the active site residues Asp 197, Glu 233, and Asp 300. Also found in this vicinity is a bound chloride ion that forms ligand interactions to Arg 195, Asn 298, and Arg 337. Domain B is the smallest (residues 100-168) and serves to form a calcium binding site against the wall of the beta-barrel of Domain A. Protein groups making ligand interactions to this calcium include Asn 100, Arg 158, Asp 167, and His 201. Domain C (residues 405-496) is made up of anti-parallel beta-structure and is only loosely associated with Domains A and B. It is notable that the N-terminal glutamine residue of human pancreatic alpha-amylase undergoes a posttranslational modification to form a stable pyrrolidone derivative that may provide protection against other digestive enzymes. Structure-based comparisons of human pancreatic alpha-amylase with functionally related enzymes serve to emphasize three points. Firstly, despite this approach facilitating primary sequence alignments with respect to the numerous insertions and deletions present, overall there is only approximately 15% sequence homology between the mammalian and fungal alpha-amylases. Secondly, in contrast, these same studies indicate that significant structural homology is present and of the order of approximately 70%. Thirdly, the positioning of Domain C can vary considerably between alpha-amylases. In terms of the more closely related porcine enzyme, there are four regions of polypeptide chain (residues 237-250, 304-310, 346-354, and 458-461) with significantly different conformations from those in human pancreatic alpha-amylase. At least two of these could play a role in observed differential substrate and cleavage pattern specificities between these enzymes. Similarly, amino acid differences between human pancreatic and salivary alpha-amylases have been localized and a number of these occur in the vicinity of the active site.
  Selected figure(s)  
Figure 1.
Fig. 1. Stereo drawing of a schematic representation of the polypeptide chain fold of human pancreatic a-amylase. Also indi- cated are the relative ositionings of the three structural domains presentin this protein (Domain A, residues 1-99, 169-404; Domain B, residues 100-168; Domain C, 405-496).along with locations of the calcium and chloride binding sites. N- and C-terminal ends of polypeptide chain have also been labeled N C, respectively. A central feature of struc- tureis the eight-stranded parallel &barrel that forms the bulk of Domain and is believed to contain the active site region.
Figure 4.
Fig. 4. Continued
  The above figures are reprinted from an Open Access publication published by the Protein Society: Protein Sci (1995, 4, 1730-1742) copyright 1995.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21251279 S.P, S.S.Zinjarde, S.Y.Bhargava, and A.R.Kumar (2011).
Potent α-amylase inhibitory activity of Indian Ayurvedic medicinal plants.
  BMC Complement Altern Med, 11, 5.  
21111049 X.Qin, L.Ren, X.Yang, F.Bai, L.Wang, P.Geng, G.Bai, and Y.Shen (2011).
Structures of human pancreatic α-amylase in complex with acarviostatins: Implications for drug design against type II diabetes.
  J Struct Biol, 174, 196-202.
PDB codes: 3old 3ole 3olg 3oli
20812985 K.Yamamoto, H.Miyake, M.Kusunoki, and S.Osaki (2010).
Crystal structures of isomaltase from Saccharomyces cerevisiae and in complex with its competitive inhibitor maltose.
  FEBS J, 277, 4205-4214.
PDB codes: 3a4a 3aj7
19763902 O.Prakash, and N.Jaiswal (2010).
alpha-Amylase: an ideal representative of thermostable enzymes.
  Appl Biochem Biotechnol, 160, 2401-2414.  
19476481 J.Pytelková, J.Hubert, M.Lepsík, J.Sobotník, R.Sindelka, I.Krízková, M.Horn, and M.Mares (2009).
Digestive alpha-amylases of the flour moth Ephestia kuehniella--adaptation to alkaline environment and plant inhibitors.
  FEBS J, 276, 3531-3546.  
19329633 L.J.Gourlay, I.Santi, A.Pezzicoli, G.Grandi, M.Soriani, and M.Bolognesi (2009).
Group B streptococcus pullulanase crystal structures in the context of a novel strategy for vaccine development.
  J Bacteriol, 191, 3544-3552.
PDB codes: 3faw 3fax
18951906 C.Ragunath, S.G.Manuel, V.Venkataraman, H.B.Sait, C.Kasinathan, and N.Ramasubbu (2008).
Probing the role of aromatic residues at the secondary saccharide-binding sites of human salivary alpha-amylase in substrate hydrolysis and bacterial binding.
  J Mol Biol, 384, 1232-1248.  
17729287 J.C.Marx, J.Poncin, J.P.Simorre, P.W.Ramteke, and G.Feller (2008).
The noncatalytic triad of alpha-amylases: a novel structural motif involved in conformational stability.
  Proteins, 70, 320-328.  
18613721 S.Cheluvaraja, M.Mihailescu, and H.Meirovitch (2008).
Entropy and free energy of a mobile protein loop in explicit water.
  J Phys Chem B, 112, 9512-9522.  
17592362 R.Quezada-Calvillo, C.C.Robayo-Torres, Z.Ao, B.R.Hamaker, A.Quaroni, G.D.Brayer, E.E.Sterchi, S.S.Baker, and B.L.Nichols (2007).
Luminal substrate "brake" on mucosal maltase-glucoamylase activity regulates total rate of starch digestion to glucose.
  J Pediatr Gastroenterol Nutr, 45, 32-43.  
15722449 R.Maurus, A.Begum, H.H.Kuo, A.Racaza, S.Numao, C.Andersen, J.W.Tams, J.Vind, C.M.Overall, S.G.Withers, and G.D.Brayer (2005).
Structural and mechanistic studies of chloride induced activation of human pancreatic alpha-amylase.
  Protein Sci, 14, 743-755.
PDB codes: 1xgz 1xh0 1xh1 1xh2
15356864 G.André, and V.Tran (2004).
Putative implication of alpha-amylase loop 7 in the mechanism of substrate binding and reaction products release.
  Biopolymers, 75, 95.  
15291818 K.Yamamoto, A.Nakayama, Y.Yamamoto, and S.Tabata (2004).
Val216 decides the substrate specificity of alpha-glucosidase in Saccharomyces cerevisiae.
  Eur J Biochem, 271, 3414-3420.  
15182367 N.Ramasubbu, C.Ragunath, P.J.Mishra, L.M.Thomas, G.Gyémánt, and L.Kandra (2004).
Human salivary alpha-amylase Trp58 situated at subsite -2 is critical for enzyme activity.
  Eur J Biochem, 271, 2517-2529.
PDB codes: 1jxj 1nm9
12906828 X.Robert, R.Haser, T.E.Gottschalk, F.Ratajczak, H.Driguez, B.Svensson, and N.Aghajari (2003).
The structure of barley alpha-amylase isozyme 1 reveals a novel role of domain C in substrate recognition and binding: a pair of sugar tongs.
  Structure, 11, 973-984.
PDB codes: 1ht6 1p6w
12021442 N.Aghajari, G.Feller, C.Gerday, and R.Haser (2002).
Structural basis of alpha-amylase activation by chloride.
  Protein Sci, 11, 1435-1441.
PDB codes: 1jd7 1jd9 1l0p
11257505 E.A.MacGregor, S.Janecek, and B.Svensson (2001).
Relationship of sequence and structure to specificity in the alpha-amylase family of enzymes.
  Biochim Biophys Acta, 1546, 1.  
11737209 H.Mori, K.S.Bak-Jensen, T.E.Gottschalk, M.S.Motawia, I.Damager, B.L.Møller, and B.Svensson (2001).
Modulation of activity and substrate binding modes by mutation of single and double subsites +1/+2 and -5/-6 of barley alpha-amylase 1.
  Eur J Biochem, 268, 6545-6558.  
10769135 G.D.Brayer, G.Sidhu, R.Maurus, E.H.Rydberg, C.Braun, Y.Wang, N.T.Nguyen, C.M.Overall, and S.G.Withers (2000).
Subsite mapping of the human pancreatic alpha-amylase active site through structural, kinetic, and mutagenesis techniques.
  Biochemistry, 39, 4778-4791.
PDB codes: 1cpu 2cpu 3cpu
11150610 J.E.Nielsen, and T.V.Borchert (2000).
Protein engineering of bacterial alpha-amylases.
  Biochim Biophys Acta, 1543, 253-274.  
11137459 J.Iulek, O.L.Franco, M.Silva, C.T.Slivinski, C.Bloch, D.J.Rigden, and M.F.Grossi de Sá (2000).
Purification, biochemical characterisation and partial primary structure of a new alpha-amylase inhibitor from Secale cereale (rye).
  Int J Biochem Cell Biol, 32, 1195-1204.  
10792537 L.Janda, J.Damborský, M.Petrícek, J.Spízek, and P.Tichý (2000).
Molecular characterization of the Thermomonospora curvata aglA gene encoding a thermotolerant alpha-1,4-glucosidase.
  J Appl Microbiol, 88, 773-783.  
  10091666 E.H.Rydberg, G.Sidhu, H.C.Vo, J.Hewitt, H.C.Côte, Y.Wang, S.Numao, R.T.MacGillivray, C.M.Overall, G.D.Brayer, and S.G.Withers (1999).
Cloning, mutagenesis, and structural analysis of human pancreatic alpha-amylase expressed in Pichia pastoris.
  Protein Sci, 8, 635-643.
PDB code: 1bsi
10547530 G.André, A.Buléon, R.Haser, and V.Tran (1999).
Amylose chain behavior in an interacting context. III. Complete occupancy of the AMY2 barley alpha-amylase cleft and comparison with biochemical data.
  Biopolymers, 50, 751-762.  
10194383 G.Feller, D.d'Amico, and C.Gerday (1999).
Thermodynamic stability of a cold-active alpha-amylase from the Antarctic bacterium Alteromonas haloplanctis.
  Biochemistry, 38, 4613-4619.  
10082956 S.Darnis, N.Juge, X.J.Guo, G.Marchis-Mouren, A.Puigserver, and J.C.Chaix (1999).
Molecular cloning and primary structure analysis of porcine pancreatic alpha-amylase.
  Biochim Biophys Acta, 1430, 281-289.  
9558324 A.K.Schmidt, S.Cottaz, H.Driguez, and G.E.Schulz (1998).
Structure of cyclodextrin glycosyltransferase complexed with a derivative of its main product beta-cyclodextrin.
  Biochemistry, 37, 5909-5915.
PDB code: 3cgt
9634702 F.Vallée, A.Kadziola, Y.Bourne, M.Juy, K.W.Rodenburg, B.Svensson, and R.Haser (1998).
Barley alpha-amylase bound to its endogenous protein inhibitor BASI: crystal structure of the complex at 1.9 A resolution.
  Structure, 6, 649-659.
PDB code: 1ava
9589808 K.Lorentz (1998).
Approved recommendation on IFCC methods for the measurement of catalytic concentration of enzymes. Part 9. IFCC method for alpha-amylase (1,4-alpha-D-glucan 4-glucanohydrolase, EC International Federation of Clinical Chemistry and Laboratory Medicine (IFCC). Committee on Enzymes.
  Clin Chem Lab Med, 36, 185-203.  
  9541387 N.Aghajari, G.Feller, C.Gerday, and R.Haser (1998).
Crystal structures of the psychrophilic alpha-amylase from Alteromonas haloplanctis in its native form and complexed with an inhibitor.
  Protein Sci, 7, 564-572.
PDB codes: 1aqh 1aqm
9862804 N.Aghajari, G.Feller, C.Gerday, and R.Haser (1998).
Structures of the psychrophilic Alteromonas haloplanctis alpha-amylase give insights into cold adaptation at a molecular level.
  Structure, 6, 1503-1516.
PDB code: 1b0i
  9416598 K.S.Devulapalle, S.D.Goodman, Q.Gao, A.Hemsley, and G.Mooser (1997).
Knowledge-based model of a glucosyltransferase from the oral bacterial group of mutans streptococci.
  Protein Sci, 6, 2489-2493.  
  9385631 M.Qian, S.Spinelli, H.Driguez, and F.Payan (1997).
Structure of a pancreatic alpha-amylase bound to a substrate analogue at 2.03 A resolution.
  Protein Sci, 6, 2285-2296.
PDB code: 1jfh
9352636 T.Suganuma, Y.Maeda, K.Kitahara, and T.Nagahama (1997).
Study of the action of human salivary alpha-amylase on 2-chloro-4-nitrophenyl alpha-maltotrioside in the presence of potassium thiocyanate.
  Carbohydr Res, 303, 219-227.  
8944767 M.Alkazaz, V.Desseaux, G.Marchis-Mouren, F.Payan, E.Forest, and M.Santimone (1996).
The mechanism of porcine pancreatic alpha-amylase. Kinetic evidence for two additional carbohydrate-binding sites.
  Eur J Biochem, 241, 787-796.  
  8897615 N.Aghajari, G.Feller, C.Gerday, and R.Haser (1996).
Crystallization and preliminary X-ray diffraction studies of alpha-amylase from the antarctic psychrophile Alteromonas haloplanctis A23.
  Protein Sci, 5, 2128-2129.  
  8819167 P.M.Matias, J.Morais, R.Coelho, M.A.Carrondo, K.Wilson, Z.Dauter, and L.Sieker (1996).
Cytochrome c3 from Desulfovibrio gigas: crystal structure at 1.8 A resolution and evidence for a specific calcium-binding site.
  Protein Sci, 5, 1342-1354.
PDB code: 1wad
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.