1r55

Crystal structure of the catalytic domain of human ADAM 33Crystal structure of the catalytic domain of human ADAM 33

Structural highlights

1r55 is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.58Å
Ligands:	, , , , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

ADA33_HUMAN Genetic variations in ADAM33 are associated with susceptibility to asthma (ASTHMA) [MIM:600807. The most common chronic disease affecting children and young adults. It is a complex genetic disorder with a heterogeneous phenotype, largely attributed to the interactions among many genes and between these genes and the environment. It is characterized by recurrent attacks of paroxysmal dyspnea, with weezing due to spasmodic contraction of the bronchi.^[1] ^[2] ^[3]

Function

ADA33_HUMAN

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

Adam33 is a putative asthma susceptibility gene encoding for a membrane-anchored metalloprotease belonging to the ADAM family. The ADAMs (a disintegrin and metalloprotease) are a family of glycoproteins implicated in cell-cell interactions, cell fusion, and cell signaling. We have determined the crystal structure of the Adam33 catalytic domain in complex with the inhibitor marimastat and the inhibitor-free form. The structures reveal the polypeptide fold and active site environment resembling that of other metalloproteases. The substrate-binding site contains unique features that allow the structure-based design of specific inhibitors of this enzyme.

Crystal structure of the catalytic domain of human ADAM33.,Orth P, Reichert P, Wang W, Prosise WW, Yarosh-Tomaine T, Hammond G, Ingram RN, Xiao L, Mirza UA, Zou J, Strickland C, Taremi SS, Le HV, Madison V J Mol Biol. 2004 Jan 2;335(1):129-37. PMID:14659745^[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Van Eerdewegh P, Little RD, Dupuis J, Del Mastro RG, Falls K, Simon J, Torrey D, Pandit S, McKenny J, Braunschweiger K, Walsh A, Liu Z, Hayward B, Folz C, Manning SP, Bawa A, Saracino L, Thackston M, Benchekroun Y, Capparell N, Wang M, Adair R, Feng Y, Dubois J, FitzGerald MG, Huang H, Gibson R, Allen KM, Pedan A, Danzig MR, Umland SP, Egan RW, Cuss FM, Rorke S, Clough JB, Holloway JW, Holgate ST, Keith TP. Association of the ADAM33 gene with asthma and bronchial hyperresponsiveness. Nature. 2002 Jul 25;418(6896):426-30. Epub 2002 Jul 10. PMID:12110844 doi:10.1038/nature00878
↑ Kedda MA, Duffy DL, Bradley B, O'Hehir RE, Thompson PJ. ADAM33 haplotypes are associated with asthma in a large Australian population. Eur J Hum Genet. 2006 Sep;14(9):1027-36. Epub 2006 Jun 14. PMID:16773130 doi:10.1038/sj.ejhg.5201662
↑ Blakey JD, Sayers I, Ring SM, Strachan DP, Hall IP. Positionally cloned asthma susceptibility gene polymorphisms and disease risk in the British 1958 Birth Cohort. Thorax. 2009 May;64(5):381-7. doi: 10.1136/thx.2008.102053. Epub 2009 Feb 22. PMID:19237393 doi:10.1136/thx.2008.102053
↑ Orth P, Reichert P, Wang W, Prosise WW, Yarosh-Tomaine T, Hammond G, Ingram RN, Xiao L, Mirza UA, Zou J, Strickland C, Taremi SS, Le HV, Madison V. Crystal structure of the catalytic domain of human ADAM33. J Mol Biol. 2004 Jan 2;335(1):129-37. PMID:14659745

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OCA

[1] Van Eerdewegh P, Little RD, Dupuis J, Del Mastro RG, Falls K, Simon J, Torrey D, Pandit S, McKenny J, Braunschweiger K, Walsh A, Liu Z, Hayward B, Folz C, Manning SP, Bawa A, Saracino L, Thackston M, Benchekroun Y, Capparell N, Wang M, Adair R, Feng Y, Dubois J, FitzGerald MG, Huang H, Gibson R, Allen KM, Pedan A, Danzig MR, Umland SP, Egan RW, Cuss FM, Rorke S, Clough JB, Holloway JW, Holgate ST, Keith TP. Association of the ADAM33 gene with asthma and bronchial hyperresponsiveness. Nature. 2002 Jul 25;418(6896):426-30. Epub 2002 Jul 10. PMID:12110844 doi:10.1038/nature00878

[2] Kedda MA, Duffy DL, Bradley B, O'Hehir RE, Thompson PJ. ADAM33 haplotypes are associated with asthma in a large Australian population. Eur J Hum Genet. 2006 Sep;14(9):1027-36. Epub 2006 Jun 14. PMID:16773130 doi:10.1038/sj.ejhg.5201662

[3] Blakey JD, Sayers I, Ring SM, Strachan DP, Hall IP. Positionally cloned asthma susceptibility gene polymorphisms and disease risk in the British 1958 Birth Cohort. Thorax. 2009 May;64(5):381-7. doi: 10.1136/thx.2008.102053. Epub 2009 Feb 22. PMID:19237393 doi:10.1136/thx.2008.102053

[4] Orth P, Reichert P, Wang W, Prosise WW, Yarosh-Tomaine T, Hammond G, Ingram RN, Xiao L, Mirza UA, Zou J, Strickland C, Taremi SS, Le HV, Madison V. Crystal structure of the catalytic domain of human ADAM33. J Mol Biol. 2004 Jan 2;335(1):129-37. PMID:14659745

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