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1fgl
From Proteopedia
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CYCLOPHILIN A COMPLEXED WITH A FRAGMENT OF HIV-1 GAG PROTEIN
Overview
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 Structure
1FGL is a Protein complex structure of sequences from Homo sapiens. Active as Peptidylprolyl isomerase, with EC number 5.2.1.8 Full crystallographic information is available from OCA.
Reference
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 Mon Nov 12 16:53:05 2007
