1YTK

Crystal structure of a nicotinate phosphoribosyltransferase from Thermoplasma acidophilum with nicotinate mononucleotide

Summary for 1YTK

• Entry DOI: 10.2210/pdb1ytk/pdb
• Related: 1YTD 1YTE
• Descriptor: nicotinate phosphoribosyltransferase from Thermoplasma acidophilum, NICOTINATE MONONUCLEOTIDE, 2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL, ... (4 entities in total)
• Functional Keywords: nicotinate phosphoribosyltransferase, type ii phosphoribosyltransferase, zinc-knuckle motif, structural genomics, psi, protein structure initiative, berkeley structural genomics center, bsgc, transferase
• Biological source: Thermoplasma acidophilum
• Total number of polymer chains: 1
• Total formula weight: 44152.45

Authors

Shin, D.H.,Berkeley Structural Genomics Center (BSGC) (deposition date: 2005-02-10, release date: 2005-03-08, Last modification date: 2011-07-13)

Primary citation

Shin, D.H.,Oganesyan, N.,Jancarik, J.,Yokota, H.,Kim, R.,Kim, S.H.
Crystal structure of a nicotinate phosphoribosyltransferase from Thermoplasma acidophilum.
J.Biol.Chem., 280:18326-18335, 2005

PubMed Abstract: We have determined the crystal structure of nicotinate phosphoribosyltransferase from Themoplasma acidophilum (TaNAPRTase). The TaNAPRTase has three domains, an N-terminal domain, a central functional domain, and a unique C-terminal domain. The crystal structure revealed that the functional domain has a type II phosphoribosyltransferase fold that may be a common architecture for both nicotinic acid and quinolinic acid (QA) phosphoribosyltransferases (PRTase) despite low sequence similarity between them. Unlike QAPRTase, TaNAPRTase has a unique extra C-terminal domain containing a zinc knuckle-like motif containing 4 cysteines. The TaNAPRTase forms a trimer of dimers in the crystal. The active site pocket is formed at dimer interfaces. The complex structures with phosphoribosylpyrophosphate (PRPP) and nicotinate mononucleotide (NAMN) showed, surprisingly, that functional residues lining on the active site of TaNAPRTase are quite different from those of QAPRTase, although their substrates are quite similar to each other. The phosphate moiety of PRPP and NAMN is anchored to the phosphate-binding loops formed by backbone amides, as found in many alpha/beta barrel enzymes. The pyrophosphate moiety of PRPP is located at the entrance of the active site pocket, whereas the nicotinate moiety of NAMN is located deep inside. Interestingly, the nicotinate moiety of NAMN is intercalated between highly conserved aromatic residues Tyr(21) and Phe(138). Careful structural analyses combined with other NAPRTase sequence subfamilies reveal that TaNAPRTase represents a unique sequence subfamily of NAPRTase. The structures of TaNAPRTase also provide valuable insight for other sequence subfamilies such as pre-B cell colony-enhancing factor, known to have nicotinamide phosphoribosyltransferase activity.

PubMed: 15753098
DOI: 10.1074/jbc.M501622200

Experimental method

X-RAY DIFFRACTION (2.65 Å)