DOI: 10.1002/pro.5560031004. The three‐dimensional structures of mutants of porphobilinogen deaminase: Toward an understanding of the structural basis of acute intermittent porphyria

The three‐dimensional structures of mutants of porphobilinogen deaminase: Toward an understanding of the structural basis of acute intermittent porphyria

10.1002/pro.5560031004

Crossref journal-article

Wiley

Protein Science (311)

Abstract

AbstractMutations in the human gene for the enzyme porphobilinogen deaminase give rise to an inherited disease of heme biosynthesis, acute intermittent porphyria. Knowledge of the 3‐dimensionai structure of human porphobilinogen deaminase, based on the structure of the bacterial enzyme, allows correlation of structure with gene organization and leads to an understanding of the relationship between mutations in the gene, structural and functional changes of the enzyme, and the symptoms of the disease. Most mutations occur in exons 10 and 12, often changing amino acids in the active site. Several of these are shown to be involved in binding the primer or substrate; none modifies Asp 84, which is essential for catalytic activity.

Bibliography

Brownlie, P. D., Cooper, J. B., Wood, S. P., Lambert, R., Blundell, T. L., Louie, G. V., Jordan, P. M., & Warren, M. J. (1994). The threeâdimensional structures of mutants of porphobilinogen deaminase: Toward an understanding of the structural basis of acute intermittent porphyria. Protein Science, 3(10), 1644â1650. Portico.

Authors 8

Paul D. Brownlie (first)
Jon B. Cooper (additional)
Steve P. Wood (additional)
Richard Lambert (additional)
Tom L. Blundell (additional)
Gordon V. Louie (additional)
Peter M. Jordan (additional)
Martin J. Warren (additional)

References 40 Referenced 58

{'key': 'e_1_2_1_2_1', 'first-page': 'S84', 'article-title': 'Effect of delta‐aminolevulinic acid on activity in the isolated hemisected mammalian spinal cord', 'volume': '21', 'author': 'Bagust J', 'year': '1985', 'journal-title': 'Neurosci Lett'} / Neurosci Lett / Effect of delta‐aminolevulinic acid on activity in the isolated hemisected mammalian spinal cord by Bagust J (1985)
10.1016/0020-711X(80)90172-X
{'key': 'e_1_2_1_4_1', 'first-page': 'A45', 'article-title': 'Acute intermittent porphyria: Identification of novel missense mutations in the human hydroxymethylbilane synthase gene', 'volume': '51', 'author': 'Chen CH', 'year': '1992', 'journal-title': 'Am J Hum Genet'} / Am J Hum Genet / Acute intermittent porphyria: Identification of novel missense mutations in the human hydroxymethylbilane synthase gene by Chen CH (1992)
10.1073/pnas.85.1.6
10.1172/JCI114869
{'key': 'e_1_2_1_7_1', 'first-page': '421', 'article-title': 'Molecular heterogeneity of acute intermittent porphyria: Identification of four additional mutations resulting in the CRIM‐negative subtype of the disease', 'volume': '49', 'author': 'Delfau MH', 'year': '1991', 'journal-title': 'Am J Hum Genet'} / Am J Hum Genet / Molecular heterogeneity of acute intermittent porphyria: Identification of four additional mutations resulting in the CRIM‐negative subtype of the disease by Delfau MH (1991)
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{'key': 'e_1_2_1_14_1', 'first-page': '660', 'article-title': 'High frequency of mutations in exon 10 of the porphobilinogen deaminase gene with crim‐positive subtypes of acute intermittent porphyria', 'volume': '51', 'author': 'Gu XF', 'year': '1992', 'journal-title': 'Am J Hum Genet'} / Am J Hum Genet / High frequency of mutations in exon 10 of the porphobilinogen deaminase gene with crim‐positive subtypes of acute intermittent porphyria by Gu XF (1992)
HartJG MillerAD LeeperFJ BattersbyAR.1987. Biosynthesis of natural porphyrins: Proof that hydroxymethyl bilane synthase (porphobilinogen deaminase) uses a novel binding group in its catalytic action.J Chem Soc Chem Commun:1762. (10.1039/c39870001762)
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{'key': 'e_1_2_1_19_1', 'first-page': '97', 'volume-title': 'The biosynthesis of the tetrapyrrole pigments', 'author': 'Lambert R', 'year': '1994'} / The biosynthesis of the tetrapyrrole pigments by Lambert R (1994)
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{'key': 'e_1_2_1_22_1', 'first-page': 'A162', 'article-title': 'A point mutation of the human porphobilinogen deaminase gene in a Swedish family with acute intermittent porphyria', 'volume': '47', 'author': 'Lee JS', 'year': '1990', 'journal-title': 'Am J Hum Genet'} / Am J Hum Genet / A point mutation of the human porphobilinogen deaminase gene in a Swedish family with acute intermittent porphyria by Lee JS (1990)
{'key': 'e_1_2_1_23_1', 'first-page': 'A28', 'article-title': 'Splice‐defective mutations of the porphobilinogen deaminase gene responsible for acute intermittent porphyria', 'volume': '42', 'author': 'Llewellyn DH', 'year': '1992', 'journal-title': 'Neth J Med'} / Neth J Med / Splice‐defective mutations of the porphobilinogen deaminase gene responsible for acute intermittent porphyria by Llewellyn DH (1992)
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{'key': 'e_1_2_1_27_1', 'first-page': 'A28', 'article-title': 'Characterisation of mutations in the human porphobilinogen deaminase gene', 'volume': '42', 'author': 'Lundin G', 'year': '1993', 'journal-title': 'Neth J Med'} / Neth J Med / Characterisation of mutations in the human porphobilinogen deaminase gene by Lundin G (1993)
{'key': 'e_1_2_1_28_1', 'first-page': '8', 'article-title': 'The “insanity” of King George III: A classic case of porphyria', 'volume': '5479', 'author': 'Macalpine I', 'year': '1966', 'journal-title': 'Br Med J'} / Br Med J / The “insanity” of King George III: A classic case of porphyria by Macalpine I (1966)
10.1007/BF00210738
10.1007/BF00420949
10.1093/hmg/3.5.809
10.3109/07853899009147275
10.1098/rspb.1990.0077
10.1093/nar/19.18.5099
10.1093/nar/14.15.5955
{'key': 'e_1_2_1_36_1', 'first-page': '631', 'article-title': 'Acute intermittent porphyria caused by a C T mutation that produces a stop codon in the porphobilinogen deaminase gene', 'volume': '87', 'author': 'Scobie GA', 'year': '1990', 'journal-title': 'Hum Genet'} / Hum Genet / Acute intermittent porphyria caused by a C T mutation that produces a stop codon in the porphobilinogen deaminase gene by Scobie GA (1990)
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10.1006/geno.1993.1005

Dates

Type	When
Created	16 years, 6 months ago (Feb. 9, 2009, 8:15 p.m.)
Deposited	1 year, 11 months ago (Sept. 27, 2023, 5:22 p.m.)
Indexed	2 months, 4 weeks ago (June 3, 2025, 3:46 p.m.)
Issued	30 years, 11 months ago (Oct. 1, 1994)
Published	30 years, 11 months ago (Oct. 1, 1994)
Published Online	16 years, 8 months ago (Dec. 31, 2008)
Published Print	30 years, 11 months ago (Oct. 1, 1994)

Funders 0

None

BibTeX

@article{Brownlie_1994, title={The three‐dimensional structures of mutants of porphobilinogen deaminase: Toward an understanding of the structural basis of acute intermittent porphyria}, volume={3}, ISSN={1469-896X}, url={http://dx.doi.org/10.1002/pro.5560031004}, DOI={10.1002/pro.5560031004}, number={10}, journal={Protein Science}, publisher={Wiley}, author={Brownlie, Paul D. and Cooper, Jon B. and Wood, Steve P. and Lambert, Richard and Blundell, Tom L. and Louie, Gordon V. and Jordan, Peter M. and Warren, Martin J.}, year={1994}, month=oct, pages={1644–1650} }

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