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Progress in Neurobiology Jul 1997During the last 10 years, adenosine deaminase (ADA), an enzyme considered to be cytosolic, has been found on the cell surface of many cells, therefore it can be... (Review)
Review
During the last 10 years, adenosine deaminase (ADA), an enzyme considered to be cytosolic, has been found on the cell surface of many cells, therefore it can be considered an ectoenzyme. EctoADA, which seems to be identical to intracellular ADA and has a globular structure, does not interact with membranes but with membrane proteins. Two of these cell surface receptors for ectoADA have been identified: CD26 and A1 adenosine receptors (A1R). Apart from degradation of extracellular adenosine another functional role of ectoADA has been assigned. EctoADA is able to transmit signals when interacting with either CD26 or A1R. In this way, it acts as a co-stimulatory molecule which facilitates a variety of specific signalling events in different cell types. The heterogeneous distribution of the enzyme in the nervous system indicates that ectoADA may be a neuroregulatory molecule. On the other hand, ectoADA might act as a bridge between two different cells thus raising the possibility that it may be important for the development of the nervous system.
Topics: Adenosine Deaminase; Animals; Cell Membrane; Membrane Proteins; Molecular Sequence Data; Sequence Homology, Amino Acid
PubMed: 9247966
DOI: 10.1016/s0301-0082(97)00013-0 -
Journal of Biomolecular Structure &... Mar 2023Malaria is a life-threatening disease in humans caused by parasites. () is one of the prevalent species found worldwide. An increase in an anti-malarial drug...
Malaria is a life-threatening disease in humans caused by parasites. () is one of the prevalent species found worldwide. An increase in an anti-malarial drug resistance suggests the urgent need for new drugs. Zn-containing adenosine deaminase (ADA) is a promising drug target because the ADA inhibition is fatal to the parasite. Malarial ADA accepts both adenosine (ADN) and 5'-methylthioadenosine (MTA) as substrates. The understanding of the substrate binding becomes crucial for an anti-malarial drug development. In this work, ADA from (pvADA) is of interest due to its prevalence worldwide. The binding of ADN and MTA are studied here using Molecular Dynamics (MD) simulations. Upon binding, the open and closed states of pvADA are captured. The displacement of 7, linking loops of 3/12, 4/13, 5/15, and /11 is involved in the cavity closure and opening. Also, the inappropriate substrate orientation induces a failure in a complete cavity closure. Interactions with D46, D172, S280, D310, and D311 are important for ADN binding, whereas only hydrogen bonds with D172 and D311 are sufficient to anchor MTA inside the pocket. No Zn-coordinated histidine residues is acquired for substrate binding. D172 is found to play a role in ribose moiety recognition, while D311 is crucial for trapping the amine group of an adenine ring towards the Zn site. Comparing between ADN and MTA, the additional interaction between D310 and an amine nitrogen on ADN supports a tighter fit that may facilitate the deamination.Communicated by Ramaswamy H. Sarma.
Topics: Humans; Adenosine; Plasmodium vivax; Adenosine Deaminase; Antimalarials; Plasmodium falciparum; Malaria; Molecular Dynamics Simulation; Amines; Malaria, Vivax
PubMed: 34994283
DOI: 10.1080/07391102.2021.2021989 -
The European Respiratory Journal Apr 1996
Topics: Adenosine Deaminase; Communicable Diseases; Humans; Immunity; Isoenzymes
PubMed: 8726922
DOI: 10.1183/09031936.96.09040632 -
Nihon Rinsho. Japanese Journal of... Aug 1999
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Nihon Rinsho. Japanese Journal of... Feb 1995
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Immunology and Allergy Clinics of North... May 2010Adenosine deaminase (ADA)-deficient severe combined immunodeficiency (SCID) comprises approximately 10% to 15% of all cases of SCID. The clinical effects of ADA... (Review)
Review
Adenosine deaminase (ADA)-deficient severe combined immunodeficiency (SCID) comprises approximately 10% to 15% of all cases of SCID. The clinical effects of ADA deficiency are manifest most dramatically in the immune system, where it leads to severe lymphopenia. Although hematopoietic stem cell transplantation remains the mainstay of treatment for ADA-deficient SCID, 2 other treatment options are available, namely enzyme replacement therapy with PEG-ADA and autologous hematopoietic stem cell gene therapy. In this article the author reviews the available data on treatment by these different options, and offers an overview on when each of the different treatment options should be used.
Topics: Adenosine Deaminase; Animals; Bone Marrow Transplantation; Clinical Trials as Topic; Enzyme Replacement Therapy; Genetic Therapy; Hematopoietic Stem Cell Transplantation; Humans; International Cooperation; Lymphopenia; Severe Combined Immunodeficiency
PubMed: 20493398
DOI: 10.1016/j.iac.2010.01.002 -
Ryoikibetsu Shokogun Shirizu 2000
Review
Topics: Adenosine Deaminase; Bone Marrow Transplantation; Diagnosis, Differential; Genetic Therapy; Humans; Mutation; Prognosis; Severe Combined Immunodeficiency
PubMed: 11212730
DOI: No ID Found -
Ryoikibetsu Shokogun Shirizu 2001
Review
Topics: Adenosine Deaminase; Adult; Child; Child, Preschool; Humans; Severe Combined Immunodeficiency
PubMed: 11462375
DOI: No ID Found -
Ryoikibetsu Shokogun Shirizu 1998
Review
Topics: Adenosine Deaminase; Hematopoietic Stem Cell Transplantation; Humans; Prognosis; Severe Combined Immunodeficiency
PubMed: 9833480
DOI: No ID Found -
Acta Crystallographica. Section D,... Jan 2022Homo sapiens adenosine deaminase 1 (HsADA1; UniProt P00813) is an immunologically relevant enzyme with roles in T-cell activation and modulation of adenosine metabolism...
Homo sapiens adenosine deaminase 1 (HsADA1; UniProt P00813) is an immunologically relevant enzyme with roles in T-cell activation and modulation of adenosine metabolism and signaling. Patients with genetic deficiency in HsADA1 suffer from severe combined immunodeficiency, and HsADA1 is a therapeutic target in hairy cell leukemias. Historically, insights into the catalytic mechanism and the structural attributes of HsADA1 have been derived from studies of its homologs from Bos taurus (BtADA) and Mus musculus (MmADA). Here, the structure of holo HsADA1 is presented, as well as biochemical characterization that confirms its high activity and shows that it is active across a broad pH range. Structurally, holo HsADA1 adopts a closed conformation distinct from the open conformation of holo BtADA. Comparison of holo HsADA1 and MmADA reveals that MmADA also adopts a closed conformation. These findings challenge previous assumptions gleaned from BtADA regarding the conformation of HsADA1 that may be relevant to its immunological interactions, particularly its ability to bind adenosine receptors. From a broader perspective, the structural analysis of HsADA1 presents a cautionary tale for reliance on homologs to make structural inferences relevant to applications such as protein engineering or drug development.
Topics: Adenosine Deaminase; Animals; Catalysis; Cattle; Crystallography, X-Ray; Humans; Hydrogen-Ion Concentration; Mice; Models, Molecular; Molecular Structure; Primary Immunodeficiency Diseases; Protein Conformation; Receptors, Purinergic P1
PubMed: 34981765
DOI: 10.1107/S2059798321011785