2fqw

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2fqw, resolution 1.71Å

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PnrA from Treponema pallidum as purified from E. coli (bound to inosine)

Overview

Treponema pallidum, the bacterial agent of syphilis, cannot be cultivated, in vitro. This constraint has severely impeded the study of the membrane, biology of this complex human pathogen. A structure-to-function approach, thus was adopted as a means of discerning the likely function of Tp0319, a, 35-kDa cytoplasmic membrane-associated lipoprotein of T. pallidum formerly, designated as TmpC. A 1.7-A crystal structure showed that recombinant, Tp0319 (rTp0319) consists of two alpha/beta domains, linked by three, crossovers, with a deep cleft between them akin to ATP-binding cassette, (ABC) receptors. In the cleft, a molecule of inosine was bound. Isothermal, titration calorimetry demonstrated that rTp0319 specifically binds purine, nucleosides (dissociation constant (Kd) approximately 10(-7) M). This, predilection for purine nucleosides by rTp0319 is consistent with its, likely role as a receptor component of a cytoplasmic membrane-associated, transporter system. Reverse transcription-PCR analysis of RNA isolated, from rabbit tissue-extracted T. pallidum additionally showed that tp0319, is transcriptionally linked to four other downstream open reading frames, thereby supporting the existence of an ABC-like operon (tp0319-0323). We, herein thus re-name tp0319 as purine nucleoside receptor A (pnrA), with, its operonic partners tp0320-0323 designated as pnrB-E, respectively. Our, study not only infers that PnrA transports purine nucleosides essential, for the survival of T. pallidum within its obligate human host, but to our, knowledge, this is the first description of an ABC-type nucleoside, transport system in any bacterium. PnrA has been grouped with a, functionally uncharacterized protein family (HBG016869), thereby implying, that other members of the family may have similar nucleoside-binding, function(s).

About this Structure

2FQW is a Single protein structure of sequence from Treponema pallidum with NOS as ligand. Full crystallographic information is available from OCA.

Reference

The PnrA (Tp0319; TmpC) lipoprotein represents a new family of bacterial purine nucleoside receptor encoded within an ATP-binding cassette (ABC)-like operon in Treponema pallidum., Deka RK, Brautigam CA, Yang XF, Blevins JS, Machius M, Tomchick DR, Norgard MV, J Biol Chem. 2006 Mar 24;281(12):8072-81. Epub 2006 Jan 16. PMID:16418175

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