Dataset Information

Crystallization of human nicotinamide phosphoribosyltransferase.

ABSTRACT: In the NAD biosynthetic pathway, nicotinamide phosphoribosyltransferase (NMPRTase; EC 2.4.2.12) plays an important role in catalyzing the synthesis of nicotinamide mononucleotide from nicotinamide and 5'-phosphoribosyl-1'-pyrophosphate. Because the diffraction pattern of the initially obtained crystals was not suitable for structure analysis, the crystal quality was improved by successive use of the microseeding technique. The resultant crystals diffracted to 2.0 A resolution. These crystals belonged to space group P21, with unit-cell parameters a = 60.56, b = 106.40, c = 82.78 A. Here, the crystallization of human NMPRTase is reported in the free form; the crystals should be useful for inhibitor-soaking experiments on the enzyme.

SUBMITTER: Takahashi R

PROVIDER: S-EPMC2335003 | biostudies-literature | 2007 May

REPOSITORIES: biostudies-literature

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Crystallization of human nicotinamide phosphoribosyltransferase.

Takahashi Ryo R Nakamura Shota S Yoshida Takuya T Kobayashi Yuji Y Ohkubo Tadayasu T

Acta crystallographica. Section F, Structural biology and crystallization communications 20070406 Pt 5

In the NAD biosynthetic pathway, nicotinamide phosphoribosyltransferase (NMPRTase; EC 2.4.2.12) plays an important role in catalyzing the synthesis of nicotinamide mononucleotide from nicotinamide and 5'-phosphoribosyl-1'-pyrophosphate. Because the diffraction pattern of the initially obtained crystals was not suitable for structure analysis, the crystal quality was improved by successive use of the microseeding technique. The resultant crystals diffracted to 2.0 A resolution. These crystals bel ...[more]

PMID: 17565174

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Project description:BACKGROUND:Postoperative hypophosphatemia is common and is associated with a lower risk of liver failure after hepatectomy, but higher morbidity after pancreatectomy. Whether different physiologic mechanisms underlie the hypophosphatemia associated with these very different clinical outcomes is unclear. This study aims to evaluate the underlying mechanism in postoperative hypophosphatemia. STUDY DESIGN:We prospectively enrolled 120 patients who underwent major hepatectomy (n = 30), minor hepatectomy (n = 30), pancreatectomy (n = 30), and laparotomy without resection (control group, n = 30). Preoperative and postoperative serum and urinary phosphorus, calcium, and creatinine, as well as phosphaturic factors, including serum nicotinamide phosphoribosyltransferase (NAMPT), fibroblast growth factor-23, and parathyroid hormone were measured. In addition, we evaluated urinary levels of nicotinamide catabolites, N-methyl-2-pyridone-5-carboxamide and N-methyl-4-pyridone-3-carboxamide. RESULTS:We found that significant hypophosphatemia occurred from postoperative day (POD) 1 to POD 2 in all 4 groups and was preceded by hyperphosphaturia from preoperative day to POD 1. Phosphate level alterations were associated with a significant increase in NAMPT levels from preoperative day to POD 2 in all 3 resected groups, but not in the control group. The fibroblast growth factor-23 levels were significantly decreased postoperatively in all 4 groups, and parathyroid hormone levels did not change in any of the 4 groups. Urine levels of N-methyl-2-pyridone-5-carboxamide and N-methyl-4-pyridone-3-carboxamide decreased significantly in all 4 groups postoperatively. CONCLUSIONS:This study demonstrates that the mechanism of hypophosphatemia is the same for both liver and pancreas resections. Postoperative hypophosphatemia is associated with increased NAMPT. The mechanism that upregulates NAMPT and its role on disparate clinical outcomes in postoperative patients warrant additional investigation.

Dataset Information

Crystallization of human nicotinamide phosphoribosyltransferase.

Publications

Crystallization of human nicotinamide phosphoribosyltransferase.

Similar Datasets

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