1yw5

From Proteopedia

Revision as of 02:29, 25 November 2007

Peptidyl-prolyl isomerase ESS1 from Candida albicans

Overview

Ess1 is a peptidyl-prolyl cis/trans isomerase (PPIase) that binds to the, carboxy-terminal domain (CTD) of RNA polymerase II. Ess1 is thought to, function by inducing conformational changes in the CTD that control the, assembly of cofactor complexes on the transcription unit. Ess1 (also, called Pin1) is highly conserved throughout the eukaryotic kingdom and is, required for growth in some species, including the human fungal pathogen, Candida albicans. Here we report the crystal structure of the C., albicansEss1 protein, determined at 1.6 A resolution. The structure, reveals two domains, the WW and the isomerase domain, that have, conformations essentially identical to those of human Pin1. However, the, linker region that joins the two domains is quite different. In human, Pin1, this linker is short and flexible, and part of it is unstructured., In contrast, the fungal Ess1 linker is highly ordered and contains a long, alpha-helix. This structure results in a rigid juxtaposition of the WW and, isomerase domains, in an orientation that is distinct from that observed, in Pin1, and that eliminates a hydrophobic pocket between the domains that, was implicated as the main substrate recognition site. These differences, suggest distinct modes of interaction with long substrate molecules, such, as the CTD of RNA polymerase II. We also show that C. albicans ess1(-)(), mutants are attenuated for in vivo survival in mice. Together, these, results suggest that CaEss1 might constitute a useful antifungal drug, target, and that structural differences between the fungal and human, enzymes could be exploited for drug design.

About this Structure

1YW5 is a Single protein structure of sequence from Candida albicans. Active as Peptidylprolyl isomerase, with EC number 5.2.1.8 Full crystallographic information is available from OCA.

Reference

The structure of the Candida albicans Ess1 prolyl isomerase reveals a well-ordered linker that restricts domain mobility., Li Z, Li H, Devasahayam G, Gemmill T, Chaturvedi V, Hanes SD, Van Roey P, Biochemistry. 2005 Apr 26;44(16):6180-9. PMID:15835905

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