Biomedical Engineering Reference
In-Depth Information
Trp
178
Leu
359
Arg
513
His
90
Tyr
355
Asp
151
Ala
516
Arg
120
Glu
119
F
NH
2
Arg
152
F
Ile
222
N
N
N
O
S
Gln
192
N
Ser
353
F
Leu
531
O
Arg
118
O
O
Arg
224
Val
523
Phe
518
Val
349
O
Arg
371
O
Gly
526
Ala
527
R
Glu
276
Glu
277
Leu
352
Tyr
406
Tyr
385
Asn
294
Arg
292
Trp
387
(A)
(B)
FIGURE 2.1
Example of a nonpolar (A) and a polar (B) binding site. In (A), the ligand, which is an analog
(R = Br) of the COX-2 inhibitor celecoxid (R = CH
3
), binds to cyclooxygenase-2 in a pocket primarily formed
by nonpolar amino acid residues (pdb-code 1CX2). In (B), the ligand, which corresponds to the active part of
the anti-inl uenza drug oseltamivir (Tamil u), binds to an inl uenza virus neuraminidase in a pocket formed
by polar residues (pdb-code 2QWK). Green arrows indicate hydrogen bonds. Green and red circles represent
nonpolar and polar residues, respectively. The dotted lines illustrate the shape of the binding sites.
180
LEU 178
1.1 Å
135
90
45
2.0 Å
0
-45
LY S 7 6
-90
2.8 Å
-135
-180
-135
-90
-45
0
45
90
135
180
(A)
(B)
Phi (°)
FIGURE 2.2
(A) Electron density of a phenylalanine side chain at 1.1, 2.0, and 2.8 Å resolution, respectively.
(B) Ramachandran plot of a protein. Two residues (Lys76 and Leu178) adopt unfavorable backbone conforma-
tions. The majority of the residues are located in the dark gray regions corresponding to favorable backbone
conformations.
