Structure of the Canine Pancreatic Lipase Gene

Mickel, F S; Weidenbach, F.; Swarovsky, B; LaForge, K. Steven; Scheele, George A.

doi:10.1016/s0021-9258(18)51572-6

Cited by 63 publications

(4 citation statements)

References 59 publications

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“…1 H NMR (CDCl 3 ): δ 5.39 (dd, 1 H, J 3,4 3.3, J 4,5 0.9 Hz, H-4), 5.21 (dd, 1 H, J 1,2 7.9, J 2,3 10.5 Hz, H-2), 5.00 (dd, 1 H, H-3), 4.58 (d, 1 H, H-1), 4.26 (m, 1 H, H-2′), 4.19 (dd, 1 H, J 5,6a 5.8, J 6a,6b 11.5 Hz, H-6a), 4.12 (dd, 1 H, J 5,6b 6.3 Hz, H-6b), 4.02 (dd, 1 H, J 1′a,2′ 6.4, J 1′a,1′b 8.2 Hz, H-1′a), 3.91 (ddd, 1 H, H-5), 3.90 (dd, 1 H, J 2′,3′a 4.2, J 3′a,3′b 10.6 Hz, H-3′a), 3.80 (dd, 1 H, J 1′b,2′ 4.2 Hz, H-1′b), 3.65 (dd, 1 H, J 2′,3′b 6.0 Hz, H-3′b), 2.15, 2.07, 2.05, 1.98 (4s, 12 H, 4 CH 3 CO), 1.42, 1.34 (2s, 6 H, (CH 3 ) 2 C). 13 (5). Glycoside 4 (0.647 g, 1.40 mmol) was added to a solution of catalytic sodium methylate in dry methanol (25 mL).…”

Section: Methodsmentioning

confidence: 99%

“…Three different mRNAs encoding pancreatic lipases have been found in the human pancreas (). They result from the expression of the genes of classical pancreatic lipase (HPL), pancreatic lipase related-protein 1 (HPLRP1) and pancreatic lipase related-protein 2 (HPLRP2), which have also been characterized in various species ( − ). The deduced amino acid sequences of HPLRP1 and HPLRP2 show 65 and 68% identity, respectively, with HPL, and the catalytic triad (S152, D176, and H263 in HPL) and major determinants of the tertiary structure are conserved ( , ).…”

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confidence: 99%

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Human Pancreatic Lipase-Related Protein 2 Is a Galactolipase

et al. 2004

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Human pancreatic lipase-related protein 2 (HPLRP2) was found to be expressed in the pancreas, but its biochemical properties were not investigated in detail. A recombinant HPLRP2 was produced in insect cells and the yeast Pichia pastoris and purified by cation exchange chromatography. Its substrate specificity was investigated using pH-stat and monomolecular film techniques and various lipid substrates (triglycerides, diglycerides, phospholipids, and galactolipids). Lipase activity of HPLRP2 on trioctanoin was inhibited by bile salts and poorly restored by adding colipase. In vivo, HPLRP2 therefore seems unlikely to show any lipase activity on dietary fat. In human pancreatic lipase (HPL), residues R256, D257, Y267, and K268 are involved in the stabilization of the open conformation of the lid domain, which interacts with colipase. These residues are not conserved in HPLRP2. When the corresponding mutations (R256G, D257G, Y267F, and K268E) are introduced into HPL, the effects of colipase are drastically reduced in the presence of bile salts. This may explain why colipase has such weak effects on HPLRP2. HPLRP2 displayed a very low level of activity on phospholipid micelles and monomolecular films. Its activity on monogalactosyldiglyceride monomolecular film, which was much higher, was similar to the activity of guinea pig pancreatic lipase related-protein 2, which shows the highest galactolipase activity ever measured. The physiological role of HPLRP2 suggested by the present results is the digestion of galactolipids, the most abundant lipids occurring in plant cells, and therefore, in the vegetables that are part of the human diet.

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Section: Methodsmentioning

confidence: 99%

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confidence: 99%

Human Pancreatic Lipase-Related Protein 2 Is a Galactolipase

et al. 2004

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“…For both LPL and hepatic triglyceride lipase, the human sequences were used. For the pancreatic lipase loop, the dog sequence (Mickel et al, 1989) was used because, by Chou-Fasman analysis, its structure is more similar to the LPL loop than is the human pancreatic lipase sequence, which differs from the dog sequence by four conservative amino acid substitutions.…”

Section: Methodsmentioning

confidence: 99%

Functional topology of a surface loop shielding the catalytic center in lipoprotein lipase

Faustinella¹,

Smith²,

Chan³

1992

Biochemistry

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Lipoprotein lipase (LPL), hepatic lipase, and pancreatic lipase show high sequence homology to one another. The crystal structure of pancreatic lipase suggests that it contains a trypsin-like Asp-His-Ser catalytic triad at the active center, which is shielded by a disulfide bridge-bounded surface loop that must be repositioned before the substrate can gain access to the catalytic residues. By sequence alignment, the homologous catalytic triad in LPL corresponds to Asp156-His241-Ser132, absolutely conserved residues, and the homologous surface loop to residues 217-238, a poorly conserved region. To verify these assignments, we expressed in vitro wild-type LPL and mutant LPLs having single amino acid mutations involving residue Asp156 (to His, Ser, Asn, Ala, Glu, or Gly), His241 (to Asn, Ala, Arg, Gln, or Trp), or Ser132 (to Gly, Ala, Thu, or Asp) individually. All 15 mutant LPLs were totally devoid of enzyme activity, while wild-type LPL and other mutant LPLs containing substitutions in other positions were fully active. We further replaced the 22-residue LPL loop which shields the catalytic center either partially (replacing 6 of 22 residues) or completely with the corresponding hepatic lipase loop. The partial loop-replacement chimeric LPL was found to be fully active, and the complete loop-replacement mutant had approximately 60% activity, although the primary sequence of the hepatic lipase loop is quite different. In contrast, replacement with the pancreatic lipase loop completely inactivated the enzyme. Our results are consistent with Asp156-His241-Ser132 being the catalytic triad in lipoprotein lipase.(ABSTRACT TRUNCATED AT 250 WORDS)

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“…The multiple intron and exon structure of the cholesterol esterase gene resembles more closely the organization of the genes important for lipid modification enzymes. For example, human hepatic lipase, lipoprotein lipase, cholesteryl ester transfer protein, and canine pancreatic lipase are encoded by genes containing 9, 10, 16, and 13 exons, respectively (Cai et al, 1989;Kirgessner et al" 1989;Agellon et al, 1990;Mickel et al, 1989). However, no sequence homology could be identified between the cholesterol esterase and these proteins.…”

Section: Resultsmentioning

confidence: 99%

Structure of the rat pancreatic cholesterol esterase gene

Fontaine

Carter²,

Hui³

1991

Biochemistry

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The gene encoding the rat pancreatic cholesterol esterase has been isolated and characterized. Analysis of overlapping genomic clones showed that the cholesterol esterase gene spans approximately 8 kb, containing 11 exons interrupted by 10 introns. The exons ranged in size from 83 to 201 bp except for the last exon, which was 548 bp in length. A TAAATA sequence was present at -31 nucleotides from the transcriptional initiation site. A putative pancreas-specific enhancer sequence was found at -90 bp upstream from the CAP site. Although cholesterol esterase shares three domains of similarity with cholinesterase and acetylcholinesterase, these domains were found to be localized in distinct exons of the cholesterol esterase gene. The organization of the cholesterol esterase gene suggests its divergent evolution with other members of the serine esterase gene family.

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Structure of the Canine Pancreatic Lipase Gene

Cited by 63 publications

References 59 publications

Human Pancreatic Lipase-Related Protein 2 Is a Galactolipase

Human Pancreatic Lipase-Related Protein 2 Is a Galactolipase

Functional topology of a surface loop shielding the catalytic center in lipoprotein lipase

Structure of the rat pancreatic cholesterol esterase gene

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