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'''CYCLOPHILIN A COMPLEXED WITH A FRAGMENT OF HIV-1 GAG PROTEIN''' | '''CYCLOPHILIN A COMPLEXED WITH A FRAGMENT OF HIV-1 GAG PROTEIN''' | ||
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[[Category: Schutkowski, M.]] | [[Category: Schutkowski, M.]] | ||
[[Category: Zhao, Y.]] | [[Category: Zhao, Y.]] | ||
[[Category: | [[Category: Aid]] | ||
[[Category: | [[Category: Binding protein for cyclosporin some]] | ||
[[Category: | [[Category: Cyclophilin]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 16:18:07 2008'' | |||
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Revision as of 16:18, 2 May 2008
CYCLOPHILIN A COMPLEXED WITH A FRAGMENT OF HIV-1 GAG PROTEIN
OverviewOverview
BACKGROUND: Cyclophilin A (CyPA), a receptor of the immunosuppressive drug cyclosporin A, catalyzes the cis-trans isomerization of peptidyl-prolyl bonds and is required for the infectious activity of human immunodeficiency virus type 1 (HIV-1). The crystal structure of CyPA complexed with a fragment of the HIV-1 gag protein should provide insights into the nature of CyPA-gag interactions and may suggest a role for CyPA in HIV-1 infectious activity. RESULTS: The crystal structure of CyPA complexed with a 25 amino acid peptide of HIV-1 gag capsid protein (25-mer) was determined and refined to an R factor of 0.195 at 1.8 A resolution. The sequence Ala88-Gly89-Pro90-Ile91 of the gag fragment is the major portion to bind to the active site of CyPA. Two residues of the 25-mer (Pro90-Ile91) bind to CyPA in a similar manner to two residues (Pro-Phe) of the CyPA substrate, succinyl-Ala-Ala-Pro-Phe-p-nitroanilide (AAPF). However, the N-terminus of the 25-mer (Ala88-Gly89) exhibits a different hydrogen-bonding pattern and molecular conformation than AAPF. The peptidyl-prolyl bond between Gly89 and Pro90 of the 25-mer has a trans conformation, in contrast to the cis conformation observed in other known CyPA-peptide complexes. The residue preceding proline, Gly89, has an unfavorable backbone conformation usually only adopted by glycine. CONCLUSIONS: The unfavorable backbone conformation of Gly89 of the gag 25-mer fragment suggests that binding between HIV-1 gag protein and CyPA requires a special sequence, Gly-Pro. Thus, in HIV-1 infectivity, CyPA is likely to function as a chaperone, rather than as a cis-trans isomerase. However, the observation of similarities between the C termini of the 25-mer and the substrate AAPF means that the involvement of the cis-trans isomerase activity of CyPA cannot be completely ruled out.
About this StructureAbout this Structure
1FGL is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
Cyclophilin A complexed with a fragment of HIV-1 gag protein: insights into HIV-1 infectious activity., Zhao Y, Chen Y, Schutkowski M, Fischer G, Ke H, Structure. 1997 Jan 15;5(1):139-46. PMID:9016720 Page seeded by OCA on Fri May 2 16:18:07 2008