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PDBsum entry 1kjh
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Contents |
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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Substrate shape determines specificity of recognition for HIV-1 protease: analysis of crystal structures of six substrate complexes.
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Authors
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M.Prabu-Jeyabalan,
E.Nalivaika,
C.A.Schiffer.
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Ref.
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Structure, 2002,
10,
369-381.
[DOI no: ]
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PubMed id
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Abstract
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The homodimeric HIV-1 protease is the target of some of the most effective
antiviral AIDS therapy, as it facilitates viral maturation by cleaving ten
asymmetric and nonhomologous sequences in the Gag and Pol polyproteins. Since
the specificity of this enzyme is not easily determined from the sequences of
these cleavage sites alone, we solved the crystal structures of complexes of an
inactive variant (D25N) of HIV-1 protease with six peptides that correspond to
the natural substrate cleavage sites. When the protease binds to its substrate
and buries nearly 1000 A2 of surface area, the symmetry of the protease is
broken, yet most internal hydrogen bonds and waters are conserved. However, no
substrate side chain hydrogen bond is conserved. Specificity of HIV-1 protease
appears to be determined by an asymmetric shape rather than a particular amino
acid sequence.
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Figure 4.
Figure 4. Conserved Water Structure(A) Fifty-two water
molecules that are conserved in at least four of the five
structures determined to 2.0 Å resolution and form at least two
protein-hydrogen bonds. Those waters found in both monomers are
labeled in bold, and only one of the two is labeled to improve
clarity. Equivalent clusters of waters are colored the same.
Those waters around the substrate peptide are shown in white
(Figure 2). Waters around the P1-loop and the tip of the flap
are shown in yellow.(B) On either side of the P1-loop, the
conserved waters are shown in blue (C) and red (D). Hydrogen
bonds between the protein and water are shown in bold, while
hydrogen bonds between nearby protein atoms are shown in dashed
lines.
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The above figure is
reprinted
by permission from Cell Press:
Structure
(2002,
10,
369-381)
copyright 2002.
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