PDBsum entry 3uqb

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Isomerase, protein binding PDB id
Protein chain
191 a.a.
Waters ×163
PDB id:
Name: Isomerase, protein binding
Title: Crystal structure of a smt fusion peptidyl-prolyl cis-trans with surface mutation d44g from burkholderia pseudomallei c with fk506
Structure: Ubiquitin-like protein smt3, peptidyl-prolyl cis- isomerase. Chain: a. Fragment: q12306 residues 13-98, q3jk38 residues 2-113. Engineered: yes. Mutation: yes. Other_details: fusion protein
Source: Burkholderia pseudomallei, saccharomyc cerevisiae. Baker's yeast. Organism_taxid: 320372, 559292. Strain: 1710b, s288c. Gene: burps1710b_a0907, smt3, ydr510w, d9719.15. Expressed in: escherichia coli. Expression_system_taxid: 469008.
1.90Å     R-factor:   0.172     R-free:   0.228
Authors: Seattle Structural Genomics Center For Infectious Disease (S
Key ref: D.W.Begley et al. (2014). A structural biology approach enables the development of antimicrobials targeting bacterial immunophilins. Antimicrob Agents Chemother, 58, 1458-1467. PubMed id: 24366729 DOI: 10.1128/AAC.01875-13
19-Nov-11     Release date:   30-Nov-11    
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Protein chain
Pfam   ArchSchema ?
Q12306  (SMT3_YEAST) -  Ubiquitin-like protein SMT3
101 a.a.
191 a.a.*
Protein chain
Pfam   ArchSchema ?
Q3JK38  (Q3JK38_BURP1) -  Peptidyl-prolyl cis-trans isomerase
113 a.a.
191 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 4 residue positions (black crosses)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     protein folding   2 terms 
  Biochemical function     isomerase activity     3 terms  


DOI no: 10.1128/AAC.01875-13 Antimicrob Agents Chemother 58:1458-1467 (2014)
PubMed id: 24366729  
A structural biology approach enables the development of antimicrobials targeting bacterial immunophilins.
D.W.Begley, D.Fox, D.Jenner, C.Juli, P.G.Pierce, J.Abendroth, M.Muruthi, K.Safford, V.Anderson, K.Atkins, S.R.Barnes, S.O.Moen, A.C.Raymond, R.Stacy, P.J.Myler, B.L.Staker, N.J.Harmer, I.H.Norville, U.Holzgrabe, M.Sarkar-Tyson, T.E.Edwards, D.D.Lorimer.
Macrophage infectivity potentiators (Mips) are immunophilin proteins and essential virulence factors for a range of pathogenic organisms. We applied a structural biology approach to characterize a Mip from Burkholderia pseudomallei (BpML1), the causative agent of melioidosis. Crystal structure and nuclear magnetic resonance analyses of BpML1 in complex with known macrocyclics and other derivatives led to the identification of a key chemical scaffold. This scaffold possesses inhibitory potency for BpML1 without the immunosuppressive components of related macrocyclic agents. Biophysical characterization of a compound series with this scaffold allowed binding site specificity in solution and potency determinations for rank ordering the set. The best compounds in this series possessed a low-micromolar affinity for BpML1, bound at the site of enzymatic activity, and inhibited a panel of homologous Mip proteins from other pathogenic bacteria, without demonstrating toxicity in human macrophages. Importantly, the in vitro activity of BpML1 was reduced by these compounds, leading to decreased macrophage infectivity and intracellular growth of Burkholderia pseudomallei. These compounds offer the potential for activity against a new class of antimicrobial targets and present the utility of a structure-based approach for novel antimicrobial drug discovery.