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PDBsum entry 1ogx

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protein ligands Protein-protein interface(s) links
Isomerase PDB id
1ogx
Jmol
Contents
Protein chains
126 a.a. *
Ligands
EQU ×2
Waters ×231
* Residue conservation analysis
PDB id:
1ogx
Name: Isomerase
Title: High resolution crystal structure of ketosteroid isomerase mutant d40n(d38n, ti numbering) from pseudomonas putida complexed with equilenin at 2.0 a resolution.
Structure: Steroid delta-isomerase. Chain: a, b. Synonym: delta-5-3-ketosteroid isomerase. Engineered: yes. Mutation: yes. Other_details: complexed with equilenin
Source: Pseudomonas putida. Organism_taxid: 303. Strain: bl21(de3). Expressed in: escherichia coli. Expression_system_taxid: 469008.
Biol. unit: Dimer (from PDB file)
Resolution:
2.0Å     R-factor:   0.198     R-free:   0.255
Authors: N.-C.Ha,M.-S.Kim,B.-H.Oh
Key ref:
N.C.Ha et al. (2000). Detection of large pKa perturbations of an inhibitor and a catalytic group at an enzyme active site, a mechanistic basis for catalytic power of many enzymes. J Biol Chem, 275, 41100-41106. PubMed id: 11007792 DOI: 10.1074/jbc.M007561200
Date:
17-May-03     Release date:   20-May-03    
Supersedes: 1e3n
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P07445  (SDIS_PSEPU) -  Steroid Delta-isomerase
Seq:
Struc:
131 a.a.
126 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.5.3.3.1  - Steroid Delta-isomerase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: A 3-oxo-Delta5-steroid = a 3-oxo-Delta4-steroid
3-oxo-Delta(5)-steroid
Bound ligand (Het Group name = EQU)
matches with 90.00% similarity
= 3-oxo-Delta(4)-steroid
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     intracellular   1 term 
  Biological process     transport   3 terms 
  Biochemical function     isomerase activity     2 terms  

 

 
    Added reference    
 
 
DOI no: 10.1074/jbc.M007561200 J Biol Chem 275:41100-41106 (2000)
PubMed id: 11007792  
 
 
Detection of large pKa perturbations of an inhibitor and a catalytic group at an enzyme active site, a mechanistic basis for catalytic power of many enzymes.
N.C.Ha, M.S.Kim, W.Lee, K.Y.Choi, B.H.Oh.
 
  ABSTRACT  
 
Delta(5)-3-Ketosteroid isomerase catalyzes cleavage and formation of a C-H bond at a diffusion-controlled limit. By determining the crystal structures of the enzyme in complex with each of three different inhibitors and by nuclear magnetic resonance (NMR) spectroscopic investigation, we evidenced the ionization of a hydroxyl group (pK(a) approximately 16.5) of an inhibitor, which forms a low barrier hydrogen bond (LBHB) with a catalytic residue Tyr(14) (pK(a) approximately 11.5), and the protonation of the catalytic residue Asp(38) with pK(a) of approximately 4.5 at pH 6.7 in the interaction with a carboxylate group of an inhibitor. The perturbation of the pK(a) values in both cases arises from the formation of favorable interactions between inhibitors and catalytic residues. The results indicate that the pK(a) difference between catalytic residue and substrate can be significantly reduced in the active site environment as a result of the formation of energetically favorable interactions during the course of enzyme reactions. The reduction in the pK(a) difference should facilitate the abstraction of a proton and thereby eliminate a large fraction of activation energy in general acid/base enzyme reactions. The pK(a) perturbation provides a mechanistic ground for the fast reactivity of many enzymes and for the understanding of how some enzymes are able to extract a proton from a C-H group with a pK(a) value as high as approximately 30.
 
  Selected figure(s)  
 
Figure 1.
Fig. 1. Dimeric structure, enzymatic reaction mechanism, and competitive inhibitors of PI. a, the dimeric structure of KSI in complex with equilenin is shown with the three critical active site residues and equilenin in a ball-and-stick model. b, the enzyme mechanism of KSI proceeding through a dienolic intermediate is shown with the catalytic residues. The H-bond between the Tyr14 OH and the oxyanion of the intermediate is indicated in a conventional way to denote a LBHB formation, the proton being in the middle of the two heavy atoms. c, the three competitive inhibitors used in this study are shown along with their markedly different pK[a] values.
Figure 3.
Fig. 3. Interaction of DC with PI. a, stereoview of the bound inhibitor and the three catalytic residues is shown along with the 2F[o] F[c] electron density map at 2.0 Å resolution contoured at 1.0 . The H-bonds and their distances are indicated. b, four possible ionization states in the interaction of DC with the catalytic residues. Whereas the first binding mode results in three charged H-bonds, the rest of the binding modes result in one charged and two neutral H-bonds.
 
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (2000, 275, 41100-41106) copyright 2000.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
22388816 K.Hotta, X.Chen, R.S.Paton, A.Minami, H.Li, K.Swaminathan, I.I.Mathews, K.Watanabe, H.Oikawa, K.N.Houk, and C.Y.Kim (2012).
Enzymatic catalysis of anti-Baldwin ring closure in polyether biosynthesis.
  Nature, 483, 355-358.
PDB code: 3rga
21308811 I.Pápai, A.Hamza, P.M.Pihko, and R.K.Wierenga (2011).
Stereoelectronic requirements for optimal hydrogen-bond-catalyzed enolization.
  Chemistry, 17, 2859-2866.  
20170220 P.Maurer, and R.Iftimie (2010).
Combining ab initio quantum mechanics with a dipole-field model to describe acid dissociation reactions in water: first-principles free energy and entropy calculations.
  J Chem Phys, 132, 074112.  
19301315 C.Li, K.E.Roege, and W.L.Kelly (2009).
Analysis of the indanomycin biosynthetic gene cluster from Streptomyces antibioticus NRRL 8167.
  Chembiochem, 10, 1064-1072.  
19799395 D.K.Chakravorty, A.V.Soudackov, and S.Hammes-Schiffer (2009).
Hybrid quantum/classical molecular dynamics simulations of the proton transfer reactions catalyzed by ketosteroid isomerase: analysis of hydrogen bonding, conformational motions, and electrostatics.
  Biochemistry, 48, 10608-10619.  
19706511 J.P.Schwans, D.A.Kraut, and D.Herschlag (2009).
Determining the catalytic role of remote substrate binding interactions in ketosteroid isomerase.
  Proc Natl Acad Sci U S A, 106, 14271-14275.  
16673426 H.Bakirci, A.L.Koner, T.Schwarzlose, and W.M.Nau (2006).
Analysis of host-assisted guest protonation exemplified for p-sulfonatocalix[4]arene--towards enzyme-mimetic pKa shifts.
  Chemistry, 12, 4799-4807.  
14747995 M.Shokhen, and A.Albeck (2004).
Is there a weak H-bond --> LBHB transition on tetrahedral complex formation in serine proteases?
  Proteins, 54, 468-477.  
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.