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PDBsum entry 1tmq

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protein metals Protein-protein interface(s) links
Hydrolase/hydrolase inhibitor PDB id
1tmq
Jmol
Contents
Protein chains
471 a.a. *
117 a.a. *
Metals
_CA
_CL
Waters ×331
* Residue conservation analysis
PDB id:
1tmq
Name: Hydrolase/hydrolase inhibitor
Title: Structure of tenebrio molitor larval alpha-amylase in complex with ragi bifunctional inhibitor
Structure: Protein (alpha-amylase). Chain: a. Protein (ragi bifunctional inhibitor). Chain: b
Source: Tenebrio molitor. Yellow mealworm. Organism_taxid: 7067. Tissue: larvae. Eleusine coracana. Finger millet. Organism_taxid: 4511. Organ: seed
Resolution:
2.50Å     R-factor:   0.191     R-free:   0.261
Authors: F.X.Gomis-Rueth,S.Strobl,R.Glockshuber
Key ref:
S.Strobl et al. (1998). A novel strategy for inhibition of alpha-amylases: yellow meal worm alpha-amylase in complex with the Ragi bifunctional inhibitor at 2.5 A resolution. Structure, 6, 911-921. PubMed id: 9687373 DOI: 10.1016/S0969-2126(98)00092-6
Date:
13-Jan-98     Release date:   02-Mar-99    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P56634  (AMY_TENMO) -  Alpha-amylase
Seq:
Struc:
471 a.a.
471 a.a.*
Protein chain
Pfam   ArchSchema ?
P01087  (IAAT_ELECO) -  Alpha-amylase/trypsin inhibitor
Seq:
Struc:
122 a.a.
117 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 2 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class: Chain A: E.C.3.2.1.1  - 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   1 term 
  Biological process     metabolic process   4 terms 
  Biochemical function     catalytic activity     9 terms  

 

 
DOI no: 10.1016/S0969-2126(98)00092-6 Structure 6:911-921 (1998)
PubMed id: 9687373  
 
 
A novel strategy for inhibition of alpha-amylases: yellow meal worm alpha-amylase in complex with the Ragi bifunctional inhibitor at 2.5 A resolution.
S.Strobl, K.Maskos, G.Wiegand, R.Huber, F.X.Gomis-Rüth, R.Glockshuber.
 
  ABSTRACT  
 
BACKGROUND: alpha-Amylases catalyze the hydrolysis of alpha-D-(1,4)-glucan linkages in starch and related compounds. There is a wide range of industrial and medical applications for these enzymes and their inhibitors. The Ragi bifunctional alpha-amylase/trypsin inhibitor (RBI) is the prototype of the cereal inhibitor superfamily and is the only member of this family that inhibits both trypsin and alpha-amylases. The mode of inhibition of alpha-amylases by these cereal inhibitors has so far been unknown. RESULTS: The crystal structure of yellow meal worm alpha-amylase (TMA) in complex with RBI was determined at 2.5 A resolution. RBI almost completely fills the substrate-binding site of TMA. Specifically, the free N terminus and the first residue (Ser1) of RBI interact with all three acidic residues of the active site of TMA (Asp185, Glu222 and Asp287). The complex is further stabilized by extensive interactions between the enzyme and inhibitor. Although there is no significant structural reorientation in TMA upon inhibitor binding, the N-terminal segment of RBI, which is highly flexible in the free inhibitor, adopts a 3(10)-helical conformation in the complex. RBI's trypsin-binding loop is located opposite the alpha-amylase-binding site, allowing simultaneous binding of alpha-amylase and trypsin. CONCLUSIONS: The binding of RBI to TMA constitutes a new inhibition mechanism for alpha-amylases and should be general for all alpha-amylase inhibitors of the cereal inhibitor superfamily. Because RBI inhibits two important digestive enzymes of animals, it constitutes an efficient plant defense protein and may be used to protect crop plants from predatory insects.
 
  Selected figure(s)  
 
Figure 1.
Figure 1. A ribbon diagram of the RBI-TMA complex. RBI is shown in gold. The three TMA domains, A (residues 1-97 and 160-379), B (residues 98-159) and C (residues 380-471), are depicted in blue, green and red, respectively. Disulfide bridges in RBI and TMA are shown in red and yellow, respectively. This figure was made with SETOR [37].
 
  The above figure is reprinted by permission from Cell Press: Structure (1998, 6, 911-921) copyright 1998.  
  Figure was selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20712044 B.Naseri, Y.Fathipour, S.Moharramipour, V.Hosseininaveh, and A.M.Gatehouse (2010).
Digestive proteolytic and amylolytic activities of Helicoverpa armigera in response to feeding on different soybean cultivars.
  Pest Manag Sci, 66, 1316-1323.  
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.  
19179285 L.Sanglas, F.X.Aviles, R.Huber, F.X.Gomis-Rüth, and J.L.Arolas (2009).
Mammalian metallopeptidase inhibition at the defense barrier of Ascaris parasite.
  Proc Natl Acad Sci U S A, 106, 1743-1747.
PDB code: 3fju
17444520 K.F.Lin, T.R.Lee, P.H.Tsai, M.P.Hsu, C.S.Chen, and P.C.Lyu (2007).
Structure-based protein engineering for alpha-amylase inhibitory activity of plant defensin.
  Proteins, 68, 530-540.
PDB code: 2gl1
16416448 P.B.Pelegrini, A.M.Murad, M.F.Grossi-de-Sá, L.V.Mello, L.A.Romeiro, E.F.Noronha, R.A.Caldas, and O.L.Franco (2006).
Structure and enzyme properties of Zabrotes subfasciatus alpha-amylase.
  Arch Insect Biochem Physiol, 61, 77-86.  
16544327 Y.J.Liu, C.S.Cheng, S.M.Lai, M.P.Hsu, C.S.Chen, and P.C.Lyu (2006).
Solution structure of the plant defensin VrD1 from mung bean and its possible role in insecticidal activity against bruchids.
  Proteins, 63, 777-786.
PDB code: 1ti5
15657043 B.C.Bønsager, P.K.Nielsen, M.Abou Hachem, K.Fukuda, M.Praetorius-Ibba, and B.Svensson (2005).
Mutational analysis of target enzyme recognition of the beta-trefoil fold barley alpha-amylase/subtilisin inhibitor.
  J Biol Chem, 280, 14855-14864.  
16279937 J.T.Christeller (2005).
Evolutionary mechanisms acting on proteinase inhibitor variability.
  FEBS J, 272, 5710-5722.  
16356852 L.Dolecková-Maresová, M.Pavlík, M.Horn, and M.Mares (2005).
De novo design of alpha-amylase inhibitor: a small linear mimetic of macromolecular proteinaceous ligands.
  Chem Biol, 12, 1349-1357.  
16356842 N.Pohl (2005).
Acyclic peptide inhibitors of amylases.
  Chem Biol, 12, 1257-1258.  
16003953 S.C.Dias, O.L.Franco, C.P.Magalhães, O.B.de Oliveira-Neto, R.A.Laumann, E.L.Figueira, F.R.Melo, and M.F.Grossi-De-Sá (2005).
Molecular cloning and expression of an alpha-amylase inhibitor from rye with potential for controlling insect pests.
  Protein J, 24, 113-123.  
12493826 R.Cazalis, T.Aussenac, L.Rhazi, A.Marin, and J.F.Gibrat (2003).
Homology modeling and molecular dynamics simulations of the N-terminal domain of wheat high molecular weight glutenin subunit 10.
  Protein Sci, 12, 34-43.  
12112856 O.Østergaard, S.Melchior, P.Roepstorff, and B.Svensson (2002).
Initial proteome analysis of mature barley seeds and malt.
  Proteomics, 2, 733-739.  
11856298 O.L.Franco, D.J.Rigden, F.R.Melo, and M.F.Grossi-De-Sá (2002).
Plant alpha-amylase inhibitors and their interaction with insect alpha-amylases.
  Eur J Biochem, 269, 397-412.  
11284678 N.Alam, S.Gourinath, S.Dey, A.Srinivasan, and T.P.Singh (2001).
Substrate-inhibitor interactions in the kinetics of alpha-amylase inhibition by ragi alpha-amylase/trypsin inhibitor (RATI) and its various N-terminal fragments.
  Biochemistry, 40, 4229-4233.  
11567160 Y.W.Chen (2001).
Solution solution: using NMR models for molecular replacement.
  Acta Crystallogr D Biol Crystallogr, 57, 1457-1461.  
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.  
10672010 K.W.Rodenburg, F.Vallée, N.Juge, N.Aghajari, X.Guo, R.Haser, and B.Svensson (2000).
Specific inhibition of barley alpha-amylase 2 by barley alpha-amylase/subtilisin inhibitor depends on charge interactions and can be conferred to isozyme 1 by mutation.
  Eur J Biochem, 267, 1019-1029.  
10759839 O.L.Franco, D.J.Rigden, F.R.Melo, C.Bloch, C.P.Silva, and M.F.Grossi de Sá (2000).
Activity of wheat alpha-amylase inhibitors towards bruchid alpha-amylases and structural explanation of observed specificities.
  Eur J Biochem, 267, 2166-2173.  
11080645 Y.W.Chen, E.J.Dodson, and G.J.Kleywegt (2000).
Does NMR mean "not for molecular replacement"? Using NMR-based search models to solve protein crystal structures.
  Structure, 8, R213-R220.  
10508777 P.J.Pereira, V.Lozanov, A.Patthy, R.Huber, W.Bode, S.Pongor, and S.Strobl (1999).
Specific inhibition of insect alpha-amylases: yellow meal worm alpha-amylase in complex with the amaranth alpha-amylase inhibitor at 2.0 A resolution.
  Structure, 7, 1079-1088.
PDB code: 1clv
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.