SuMo: A Tool for Protein Function Inference Based on 3D Structures Comparisons - Identification of Ligand Binding Site and Protein-Protein Interaction Area - page 19

Table 1.4 (continued)

Hit Id PDB Id SCF Count Sumo Score Header line of the PDB structure

42 1IYQ 17 9.79 TOHO-1 beta-lactamase

in complex with
benzylpenicillin

43 2ZD8 20 9.67 SHV-1 class a beta-lactamase

complexed with meropenem

44 1PIO 16 9.42 An engineered Staphylococcus

aureus PC1 beta-lactamase
that hydrolyses third
generation cephalosporins

45 1CK3 15 9.41 N276D mutant of Escherichia coli

TEM-1 beta-lactamase

triplet of objects, protein with same fold and very similar site as PBP protein, are
highly ranked even if the percentage of identity of sequence is very low. After PBP,
the analysis of hits reveals another set composed by betalactamase. Betalactam mol-
ecule binds on this protein and its cycle is opened by the enzyme. When the betalac-
tam cycle is open the drug loses its antibiotic effect. The protein is involved in the
mechanism of antibiotic resistance in bacteria. After line 17, entries 21 (among the
last 28) are betalactamase proteins and 7 other PBP different fromPBP-2X. The
sequence identity between the first betalactamase (code 1YLZ) (Chen et al. 2005 )
and reference PBP-2X (1QMF) is only 50/702: 7.19%. The analysis of the first beta
lactamase revealed that this protein is involved in the resistance because this enzyme
of this strain binds on penicillin drug and also third generation cephalosporin drug.
This PBP was crystallized with ceftazidime which is third generation cephalosporin.
A BLAST run was used to find proteins with similar sequence of the PBP-2X on the
sequence database of PDB model, we found all PBP-2X but no other PBP and no
betalactamase structure. The two PDB structures were superimposed by using the
Sybyl X software (Tripos 2010 ), the RMSD found was as high as 20 Å and the two
binding sites are located at the opposite directions in the fitted molecules. On the
contrary, the analysis of the superposition provided by SuMo software reveals that
mostly all objects of the sites are commonly shared by the two structures. The three
residues which could play a catalytic role have a equivalent object on the two struc-
tures, the K340 of the PBP-2X is replaced by the K73 on the betalactamase, the
S337 by S70 and S395 by S130. The superposition of the both sites resulting from
the SuMo analysis is displayed on the Fig. 1.4 .

1.4 Discussion

Since the development of the original SuMO method in 2003 (Jambon et al. 2003 ) ,
several improvements have been performed either in our team (Jambon et al. 2005 )
or by others (Sperandio et al. 2007 ), including protein-ligand interactions exposed