cd04604

Two tandem repeats of the cystathionine beta-synthase (CBS pair) domains associated with the with the SIS (Sugar ISomerase) domain

CDD entry
Member databaseCDD
CDD typedomain
Short nameCBS_pair_SIS_assoc
SetCBS_pair_SF

Description

This cd contains two tandem repeats of the cystathionine beta-synthase (CBS pair) domains associated with the SIS (Sugar ISomerase) domain in the API [A5P (D-arabinose 5-phosphate) isomerase] protein KpsF/GutQ. These APIs catalyze the conversion of the pentose pathway intermediate D-ribulose 5-phosphate into A5P, a precursor of 3-deoxy-D-manno-octulosonate, which is an integral carbohydrate component of various glycolipids coating the surface of the outer membrane of Gram-negative bacteria, including lipopolysaccharide and many group 2 K-antigen capsules. The CBS domain, named after human CBS, is a small domain originally identified in cystathionine beta-synthase and is subsequently found in a wide range of different proteins. CBS domains usually occur in tandem repeats. They associate to form a so-called Bateman domain or a CBS pair based on crystallographic studies in bacteria. The CBS pair was used as a basis for this cd hierarchy since the human CBS proteins can adopt the typical core structure and form an intramolecular CBS pair. The interface between the two CBS domains forms a cleft that is a potential ligand binding site. The CBS pair coexists with a variety of other functional domains and this has been used to help in its classification here. It has been proposed that the CBS domain may play a regulatory role, although its exact function is unknown. Mutations of conserved residues within this domain are associated with a variety of human hereditary diseases, including congenital myotonia, idiopathic generalized epilepsy, hypercalciuric nephrolithiasis, and classic Bartter syndrome (CLC chloride channel family members), Wolff-Parkinson-White syndrome (gamma 2 subunit of AMP-activated protein kinase), retinitis pigmentosa (IMP dehydrogenase-1), and homocystinuria (cystathionine beta-synthase).
[2, 9, 3, 5, 8, 6, 7, 1, 4]

References

1.Regulation of human cystathionine beta-synthase by S-adenosyl-L-methionine: evidence for two catalytically active conformations involving an autoinhibitory domain in the C-terminal region. Janosik M, Kery V, Gaustadnes M, Maclean KN, Kraus JP. Biochemistry 40, 10625-33, (2001). View articlePMID: 11524006

2.Transcriptional organization and regulation of expression of region 1 of the Escherichia coli K5 capsule gene cluster. Simpson DA, Hammarton TC, Roberts IS. J Bacteriol 178, 6466-74, (1996). PMID: 8932302

3.The structure of a domain common to archaebacteria and the homocystinuria disease protein. Bateman A. Trends Biochem. Sci. 22, 12-3, (1997). View articlePMID: 9020585

4.CBS domains form energy-sensing modules whose binding of adenosine ligands is disrupted by disease mutations. Scott JW, Hawley SA, Green KA, Anis M, Stewart G, Scullion GA, Norman DG, Hardie DG. J. Clin. Invest. 113, 274-84, (2004). View articlePMID: 14722619

5.CBS domains in CIC chloride channels implicated in myotonia and nephrolithiasis (kidney stones). Ponting CP. J. Mol. Med. 75, 160-3, (1997). PMID: 9106071

6.Characteristics and crystal structure of bacterial inosine-5'-monophosphate dehydrogenase. Zhang R, Evans G, Rotella FJ, Westbrook EM, Beno D, Huberman E, Joachimiak A, Collart FR. Biochemistry 38, 4691-700, (1999). View articlePMID: 10200156

7.Mutations in the regulatory domain of cystathionine beta synthase can functionally suppress patient-derived mutations in cis. Shan X, Dunbrack RL Jr, Christopher SA, Kruger WD. Hum Mol Genet 10, 635-43, (2001). PMID: 11230183

8.Correction of disease-causing CBS mutations in yeast. Shan X, Kruger WD. Nat Genet 19, 91-3, (1998). PMID: 9590298

9.CBS domains: structure, function, and pathology in human proteins. Ignoul S, Eggermont J. Am. J. Physiol., Cell Physiol. 289, C1369-78, (2005). View articlePMID: 16275737

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