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The reactive-center...
The reactive-center loop of active PAI-1 is folded close to the protein core and can be partially inserted
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- Hägglöf, Peter (författare)
- Umeå universitet,Institutionen för medicinsk kemi och biofysik
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- Bergström, Fredrik (författare)
- Umeå universitet,Kemiska institutionen
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- Wilczynska, Malgorzata (författare)
- Umeå universitet,Institutionen för medicinsk kemi och biofysik
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- Johansson, Lennart B-Å (författare)
- Umeå universitet,Kemiska institutionen
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- Ny, Tor (författare)
- Umeå universitet,Institutionen för medicinsk kemi och biofysik
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(creator_code:org_t)
- London : Academic Press, 2004
- 2004
- Engelska.
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Ingår i: Journal of Molecular Biology. - London : Academic Press. - 0022-2836 .- 1089-8638. ; 335:3, s. 823-832
- Relaterad länk:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Plasminogen activator inhibitor 1 (PAI-1) is the main inhibitor of plasminogen activators and plays an important role in many pathophysiological processes. Like other members of the serpin family, PAI-1 has a reactive center consisting of a mobile loop (RCL) with P1 and P1′ residues acting as a “bait” for cognate protease. In contrast to the other serpins, PAI-1 loses activity by spontaneous conversion to an inactive latent form. This involves full insertion of the RCL into β-sheet A. To search for molecular determinants that could be responsible for conversion of PAI-1 to the latent form, we studied the conformation of the RCL in active PAI-1 in solution. Intramolecular distance measurements by donor–donor energy migration and probe quenching methods reveal that the RCL is located much closer to the core of PAI-1 than has been suggested by the recently resolved X-ray structures of stable PAI-1 mutants. Disulfide bonds can be formed in double-cysteine mutants with substitutions at positions P11 or P13 of the RCL and neighboring residues in β-sheet A. This suggests that the RCL may be preinserted up to residue P13 in active PAI-1, and possibly even to residue P11. We propose that the close proximity of the RCL to the protein core, and the ability of the loop to preinsert into β-sheet A is a possible reason for PAI-1 being able to convert spontaneously to its latent form.
Ämnesord
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
Nyckelord
- fluorescence
- donor–donor energy migration
- distance measurement
- serpin
- PAI-1
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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