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-62° for HIV-1 integrase, a frequently observed rotamer. For the other three molecules this Chi 1 value
varies between -142° and -156°, a common range for rotamer angles. The preference for the first
rotamer of the HIV side chain is probably due to the 2.73 Å-long hydrogen bond between Oο°2 of
Asp64 and Nε2 of Gln62. There is no such interaction in the other molecules. The different rotamer
causes a 2.46 Å rms separation of the Cγ positions around the HIV-1 Cγ, compared to only 1.63 Å
around the Cγ of Asp443 in HIV-1 RNase H, indicting the carboxylate of Asp64 in HIV-1 integrase as
the outlier.
Position of the Second Carboxylate Residue
Page 99
In all the analogous structures, the second essential carboxylate resides just after the end of the fourth β
strand. The main-chain atoms are not involved in strand-forming direct hydrogen bonds, therefore the
chain diverts from running parallel with the first strand, forming a small cleft. The equivalent residues
are Asp116 in HIV-1, Asp498 in HIV-1 RNase H, and Glu66 in RuvC. The clustering is weaker than for
Asp64; the rms deviation is 1.77 Å in α-carbon position around the HIV-1 integrase residue.
Interestingly, by including the structurally otherwise highly homologous ASV integrase core, the rms
deviation increases to 2.15 Å due to the 3 Å distance between the Cα of Asp116 of HIV-1 integrase and
that of the corresponding residue, Asp121 of ASV integrase. The rms separation between the ASV
position and the rest of the cluster (now excluding HIV-1 integrase) is 2.2 Å, which is rather high,
identifying the ASV residue as the outlier. For the Chi 1 torsion angles, all three preferred rotamers are
present: Chi 1 is -86° for HIV-1 integrase, 73° for HIV-1 RNase H, and -173° for the MuA transposase.
The RuvC Chi 1 value is not included in this comparison because it has a Glu in this position. The
different Chi 1 values combined with the variation in α-carbon positions leads to a somewhat more
scattered Cγ (or Cδ for Glu66 in RuvC) position with an rms deviation of 2.71 Å around Cγ of Asp116
of HIV-1 integrase. By including the ASV molecule, the scatter increases to 3.82 Å due to the 6 Å
distance between Cγ of Asp116 in HIV-1 integrase and Cγ of Asp121 of ASV integrase.
The Third Essential Carboxylate
The location of the third essential catalytic carboxylate varies between different members of the
superfamily. For HIV-1 integrase, Glu152 is in a disordered region with no interpretable electron
density. Based on the location of the equivalent residue in the ASV integrase, its position is assumed to
be on helix D, as discussed above. For RNase H, Glu478 is located on helix A, with its side chain
pointing toward the other two carboxylates to complete the divalentmetal-binding site. Such metal
binding has been observed crystallographically
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