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PDBsum entry 1gl0

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protein metals Protein-protein interface(s) links
Hydrolase/inhibitor PDB id
1gl0
Jmol
Contents
Protein chains
241 a.a. *
32 a.a. *
Metals
_CD ×3
Waters ×51
* Residue conservation analysis
PDB id:
1gl0
Name: Hydrolase/inhibitor
Title: Structure of the complex between bovine alpha-chymotrypsin and pmp-d2v, an inhibitor from the insect locusta migratoria
Structure: Protease inhibitor lcmi i. Chain: i. Synonym: pmp-d2v, pars intercerebralis major peptide d2 (variant). Mutation: yes. Chymotrypsinogen a. Chain: e. Synonym: alpha-chymotrypsin. Other_details: commercially available
Source: Synthetic: yes. Locusta migratoria. Migratory locust. Organism_taxid: 7004. Organ: brain, fat body. Tissue: hemolymph. Bos taurus. Bovine. Organism_taxid: 9913.
Biol. unit: Hetero-Dimer (from PDB file)
Resolution:
3.0Å     R-factor:   0.174     R-free:   0.198
Authors: A.Roussel,C.Kellenberger
Key ref:
A.Roussel et al. (2001). Complexation of two proteic insect inhibitors to the active site of chymotrypsin suggests decoupled roles for binding and selectivity. J Biol Chem, 276, 38893-38898. PubMed id: 11495915 DOI: 10.1074/jbc.M105707200
Date:
22-Aug-01     Release date:   28-Nov-01    
PROCHECK
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 Headers
 References

Protein chain
Pfam   ArchSchema ?
P00766  (CTRA_BOVIN) -  Chymotrypsinogen A
Seq:
Struc:
245 a.a.
241 a.a.
Protein chain
Pfam   ArchSchema ?
P80060  (LCM_LOCMI) -  Protease inhibitors
Seq:
Struc:
92 a.a.
32 a.a.*
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 2 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class: Chain E: E.C.3.4.21.1  - Chymotrypsin.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Preferential cleavage: Tyr-|-Xaa, Trp-|-Xaa, Phe-|-Xaa, Leu-|-Xaa.
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     extracellular region   2 terms 
  Biological process     digestion   2 terms 
  Biochemical function     catalytic activity     7 terms  

 

 
DOI no: 10.1074/jbc.M105707200 J Biol Chem 276:38893-38898 (2001)
PubMed id: 11495915  
 
 
Complexation of two proteic insect inhibitors to the active site of chymotrypsin suggests decoupled roles for binding and selectivity.
A.Roussel, M.Mathieu, A.Dobbs, B.Luu, C.Cambillau, C.Kellenberger.
 
  ABSTRACT  
 
The crystal structures of two homologous inhibitors (PMP-C and PMP-D2v) from the insect Locusta migratoria have been determined in complex with bovine alpha-chymotrypsin at 2.1- and 3.0-A resolution, respectively. PMP-C is a potent bovine alpha-chymotrypsin inhibitor whereas native PMP-D2 is a weak inhibitor of bovine trypsin. One unique mutation at the P1 position converts PMP-D2 into a potent bovine alpha-chymotrypsin inhibitor. The two peptides have a similar overall conformation, which consists of a triple-stranded antiparallel beta-sheet connected by three disulfide bridges, thus defining a novel family of serine protease inhibitors. They have in common the protease interaction site, which is composed of the classical protease binding loop (position P5 to P'4, corresponding to residues 26-34) and of an internal segment (residues 15-18), held together by two disulfide bridges. Structural divergences between the two inhibitors result in an additional interaction site between PMP-D2v (position P10 to P6, residues 21-25) and the residues 172-175 of alpha-chymotrypsin. This unusual interaction may be responsible for species selectivity. A careful comparison of data on bound and free inhibitors (from this study and previous NMR studies, respectively) suggests that complexation to the protease stabilizes the flexible binding loop (from P5 to P'4).
 
  Selected figure(s)  
 
Figure 1.
Fig. 1. A, stereo view of the final (2F[o] F[c]) electron density map (contoured at 0.6 ) superimposed onto the final refined model of PMP-C (carbon atoms are colored in yellow, nitrogen in blue, oxygen in red, and sulfur in green) (generated with Turbo-Frodo; see Ref. 15). B, stereo view of the overall fold of PMP-C (generated with Molscript; see Ref. 29). The colors are attributed according to the temperature factors as follows: blue, 25 Å2; cornflower blue, 26-40 Å2; blue violet, 41-55 Å2; magenta, 56-75 Å2; and red, 76 Å2. C, sequences of PMP-C and PMP-D2. The residues conserved among L. migratoria, S. gregaria, and P. leniusculus sequences are highlighted with yellow.
Figure 3.
Fig. 3. A, close view of the hydrogen bond network between the binding loop and the internal segment for PMP-C (in atom-type color; see legend of Fig. 1A) and Ecotin (in dark blue), with the four residues in PMP-C labeled. B, superimposition of the crystal structure (in yellow) and the 36 models from the NMR study (in blue) of PMP-C. The r.m.s.d. from superimposition are smaller than 1 Å for regions 3-11 and 16-28 and 1.8 and 2.4 Å for regions 12-15 and 29-35, respectively.
 
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (2001, 276, 38893-38898) copyright 2001.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21053238 C.J.Farady, and C.S.Craik (2010).
Mechanisms of macromolecular protease inhibitors.
  Chembiochem, 11, 2341-2346.  
19435517 B.Breugelmans, G.Simonet, V.van Hoef, S.Van Soest, and J.Vanden Broeck (2009).
Identification, distribution and molecular evolution of the pacifastin gene family in Metazoa.
  BMC Evol Biol, 9, 97.  
18353103 B.Breugelmans, G.Simonet, V.van Hoef, I.Claeys, S.Van Soest, and J.Vanden Broeck (2008).
Quantitative RT-PCR analysis of pacifastin-related precursor transcripts during the reproductive cycle of solitarious and gregarious desert locusts.
  Insect Mol Biol, 17, 137-145.  
18514224 C.J.Farady, P.F.Egea, E.L.Schneider, M.R.Darragh, and C.S.Craik (2008).
Structure of an Fab-protease complex reveals a highly specific non-canonical mechanism of inhibition.
  J Mol Biol, 380, 351-360.
PDB code: 3bn9
19020355 P.Leone, A.Roussel, and C.Kellenberger (2008).
Structure of Locusta migratoria protease inhibitor 3 (LMPI-3) in complex with Fusarium oxysporum trypsin.
  Acta Crystallogr D Biol Crystallogr, 64, 1165-1171.
PDB code: 2vu8
16967183 J.X.Cao, J.Q.Dai, Z.M.Dai, G.L.Yin, and W.J.Yang (2007).
A male reproduction-related Kazal-type peptidase inhibitor gene in the prawn, Macrobrachium rosenbergii: molecular characterization and expression patterns.
  Mar Biotechnol (NY), 9, 45-55.  
17503165 P.Zhao, Q.Xia, J.Li, H.Fujii, Y.Banno, and Z.Xiang (2007).
Purification, characterization and cloning of a chymotrypsin inhibitor (CI-9) from the hemolymph of the silkworm, Bombyx mori.
  Protein J, 26, 349-357.  
16358328 P.Hudáky, and A.Perczel (2006).
A self-stabilized model of the chymotrypsin catalytic pocket. The energy profile of the overall catalytic cycle.
  Proteins, 62, 749-759.  
  16820690 S.Roy, P.Aravind, C.Madhurantakam, A.K.Ghosh, R.Sankaranarayanan, and A.K.Das (2006).
Crystallization and preliminary X-ray diffraction analysis of a protease inhibitor from the haemolymph of the Indian tasar silkworm Antheraea mylitta.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 62, 669-671.  
16623717 Z.Gáspári, B.Szenthe, A.Patthy, W.M.Westler, L.Gráf, and A.Perczel (2006).
Local binding with globally distributed changes in a small protease inhibitor upon enzyme binding.
  FEBS J, 273, 1831-1842.  
15654893 N.Singh, T.Jabeen, S.Sharma, I.Roy, M.N.Gupta, S.Bilgrami, R.K.Somvanshi, S.Dey, M.Perbandt, C.Betzel, A.Srinivasan, and T.P.Singh (2005).
Detection of native peptides as potent inhibitors of enzymes. Crystal structure of the complex formed between treated bovine alpha-chymotrypsin and an autocatalytically produced fragment, IIe-Val-Asn-Gly-Glu-Glu-Ala-Val-Pro-Gly-Ser-Trp-Pro-Trp, at 2.2 angstroms resolution.
  FEBS J, 272, 562-572.
PDB code: 1oxg
11856311 Z.Gáspári, A.Patthy, L.Gráf, and A.Perczel (2002).
Comparative structure analysis of proteinase inhibitors from the desert locust, Schistocerca gregaria.
  Eur J Biochem, 269, 527-537.
PDB codes: 1kgm 1kio 1kj0
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.