PDBsum entry 1ds3

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protein links
Hydrolase inhibitor PDB id
Protein chain
51 a.a. *
Waters ×41
* Residue conservation analysis
PDB id:
Name: Hydrolase inhibitor
Title: Crystal structure of omtky3-ch2-asp19i
Structure: Ovomucoid. Chain: i. Fragment: third domain (omtky3). Engineered: yes. Mutation: yes
Source: Meleagris gallopavo. Turkey. Organism_taxid: 9103. Expressed in: escherichia coli. Expression_system_taxid: 562. Other_details: the peptide bond between leu18i(2lu) and asp been reduced.
1.65Å     R-factor:   0.196     R-free:   0.230
Authors: K.S.Bateman,K.Huang,S.Anderson,W.Lu,M.A.Qasim,M.Laskowski Jr M.N.G.James
Key ref:
K.S.Bateman et al. (2001). Contribution of peptide bonds to inhibitor-protease binding: crystal structures of the turkey ovomucoid third domain backbone variants OMTKY3-Pro18I and OMTKY3-psi[COO]-Leu18I in complex with Streptomyces griseus proteinase B (SGPB) and the structure of the free inhibitor, OMTKY-3-psi[CH2NH2+]-Asp19I. J Mol Biol, 305, 839-849. PubMed id: 11162096 DOI: 10.1006/jmbi.2000.4343
06-Jan-00     Release date:   31-Jan-01    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P68390  (IOVO_MELGA) -  Ovomucoid
185 a.a.
51 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!
  Biochemical function     serine-type endopeptidase inhibitor activity     1 term  


DOI no: 10.1006/jmbi.2000.4343 J Mol Biol 305:839-849 (2001)
PubMed id: 11162096  
Contribution of peptide bonds to inhibitor-protease binding: crystal structures of the turkey ovomucoid third domain backbone variants OMTKY3-Pro18I and OMTKY3-psi[COO]-Leu18I in complex with Streptomyces griseus proteinase B (SGPB) and the structure of the free inhibitor, OMTKY-3-psi[CH2NH2+]-Asp19I.
K.S.Bateman, K.Huang, S.Anderson, W.Lu, M.A.Qasim, M.Laskowski, M.N.James.
X-ray crystallography has been used to determine the 3D structures of two complexes between Streptomyces griseus proteinase B (SGPB), a bacterial serine proteinase, and backbone variants of turkey ovomucoid third domain (OMTKY3). The natural P1 residue (Leu18I) has been substituted by a proline residue (OMTKY3-Pro18I) and in the second variant, the peptide bond between Thr17I and Leu18I was replaced by an ester bond (OMTKY3-psi[COO]-Leu18I). Both variants lack the P1 NH group that donates a bifurcated hydrogen bond to the carbonyl O of Ser214 and O(gamma) of the catalytic Ser195, one of the common interactions between serine proteinases and their canonical inhibitors. The SGPB:OMTKY3-Pro18I complex has many structural differences in the vicinity of the S1 pocket when compared with the previously determined structure of SGPB:OMTKY3-Leu18I. The result is a huge difference in the DeltaG degrees of binding (8.3 kcal/mol), only part of which can be attributed to the missing hydrogen bond. In contrast, very little structural difference exists between the complexes of SGPB:OMTKY3-psi[COO]-Leu18I and SGPB:OMTKY3-Leu18I, aside from an ester O replacing the P1 NH group. Therefore, the difference in DeltaG degrees, 1.5 kcal/mol as calculated from the measured equilibrium association constants, can be attributed to the contribution of the P1 NH hydrogen bond toward binding. A crystal structure of OMTKY3 having a reduced peptide bond between P1 Leu18I and P'1 Asp19I, (OMTKY3-psi[CH2NH2+]-Asp19I) has also been determined by X-ray crystallography. This variant has very weak association equilibrium constants with SGPB and with chymotrypsin. The structure of the free inhibitor suggests that the reduced peptide bond has not introduced any major structural changes in the inhibitor. Therefore, its poor ability to inhibit serine proteinases is likely due to the disruptions of the canonical interactions at the oxyanion hole.
  Selected figure(s)  
Figure 1.
Figure 1. Final electron density maps in the region of the S[1] substrate pocket and active site of SGPB (or in the vicinity of the reduced peptide bond for OMTKY3-Q[CH[2]NH[2]^+]-Asp19I), superimposed onto the final refined models. Map coefficients are 2|F[o]| - |F[c]| contoured at 1s (purple) and |F[o]| - |F[c]| contoured at 2.5s (green) and at -2.5s (red). Carbon atoms have been coloured yellow, nitrogen atoms blue and oxygen atoms red. (a) SGPB:OMTKY3-Pro18I; (b) SGPB:OMTKY3-Q[COO]-Leu18I; (c) OMTKY3-Q[CH[2]NH[2]^+]-Asp19I. This Figure was made with XtalView[42].
Figure 4.
Figure 4. Superimposition of the OMTKY3 variant molecules from OMTKY3-Q[CH[2]NH[2]^+]-Asp19I (violet) and SGPB:OMTKY3-Leu18I (green). All atoms have been depicted for the segment from P[4] to P[2]' (oxygen atoms are red, nitrogen atoms are blue and sulphur atoms are yellow). The remaining residues are depicted as a C^a trace.
  The above figures are reprinted by permission from Elsevier: J Mol Biol (2001, 305, 839-849) copyright 2001.  
  Figures were selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
18067154 H.Oku, K.Yamada, and R.Katakai (2008).
Conformational change from antiparallel beta-sheet to alpha-helix in a series of depsipeptide, -(Leu-Leu-Lac)(n)-: syntheses, spectroscopic studies, and crystal structures of Boc-Leu-Lac-OEt and Boc-(Leu-Leu-Lac)(n)-OEt (n = 1, 2).
  Biopolymers, 89, 270-283.  
16939283 F.I.Valiyaveetil, M.Sekedat, R.MacKinnon, and T.W.Muir (2006).
Structural and functional consequences of an amide-to-ester substitution in the selectivity filter of a potassium channel.
  J Am Chem Soc, 128, 11591-11599.
PDB codes: 2h8p 2hfe 2hg5
16463276 Z.Yi, O.Vitek, M.A.Qasim, S.M.Lu, W.Lu, M.Ranjbar, J.Li, M.C.Laskowski, C.Bailey-Kellogg, and M.Laskowski (2006).
Functional evolution within a protein superfamily.
  Proteins, 63, 697-708.  
15858268 J.T.Maynes, M.M.Cherney, M.A.Qasim, M.Laskowski, and M.N.James (2005).
Structure of the subtilisin Carlsberg-OMTKY3 complex reveals two different ovomucoid conformations.
  Acta Crystallogr D Biol Crystallogr, 61, 580-588.
PDB code: 1yu6
12581670 M.Laskowski, M.A.Qasim, and Z.Yi (2003).
Additivity-based prediction of equilibrium constants for some protein-protein associations.
  Curr Opin Struct Biol, 13, 130-139.  
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