Structure of the Calcium-Dependent Lectin Domain from a Rat Mannose-Binding Protein Determined by MAD Phasing

Weis, William I.; Kahn, Richard; Fourme, R.; Drickamer, Kurt; Hendrickson, Wayne A.

doi:10.1126/science.1721241

Cited by 548 publications

(417 citation statements)

References 52 publications

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“…The a + p fold of MutT resembles, but is not identical to, certain other members of this class of proteins such as the actin binding domain of severin (Schnuchel et al, 1995) and the carbohydrate recognition domain of a mannose binding protein (Weis et al, 1991), both of which bind Ca2+, the phosphotyrosine recognition SH2 domain (Waksman et al, 1992), and the mechanistically related enzyme inorganic pyrophosphatase (Kankare et al, 1994;Teplyakov et al, 1994) although none of these proteins show significant sequence homology to MutT (Mejean et al, 1994).…”

Section: Discussionmentioning

confidence: 99%

Solution Structure of the MutT Enzyme, a Nucleoside Triphosphate Pyrophosphohydrolase

Abeygunawardana¹,

Weber²,

Gittis³

et al. 1995

Biochemistry

124

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The MutT enzyme (129 residues) catalyzes the hydrolysis of normal and mutagenic nucleoside triphosphates, such as 8-oxo-dGTP, by substitution at the rarely attacked P-P, to yield NMP and pyrophosphate. Previous heteronuclear NMR studies of MutT have shown the secondary structure to consist of a five-stranded mixed P-sheet connected by the loop I-a-helix I-loop I1 motif, by two tight tums, and by loop 111, and terminated by loop IV-a-helix I1 (4) restraints and 34 backbone hydrogen bond restraints were used to determine the tertiary structure ofMutT by distance geometry, simulated annealing, and energy minimization with the program X-PLOR. The structure is globular and compact with the parallel portion of the P-sheet sandwiched between the two a-helices, forming an a f , ! ? fold. The essential divalent cation has previously been shown to bind near residues Gly-37, Gly-38, Lys-39, and Glu-57, and nucleotides have been shown to bind near residues Leu-54 and Val-58 by NMR relaxation methods [Frick et al. (1995) Biochemistry 34, 5577-55861. The tertiary structure of MutT shows these residues to be near each other along the loop I-helix I region of the enzyme. A cluster of five glutamate residues (41,53, 56,57, and 98) form a patch of strongly negative electrostatic potential likely constituting the metal binding site. This site is contiguous with a deep cleft between P-strands A, C, and D and loop I which may contribute to the nucleotide binding site. This location of the active site is consistent with mutagenesis studies and with sequence homologies among MutT-like pyrophosphohydrolases.The MutT enzyme, a pyrophosphohydrolase of 129 residues, catalyzes the unusual hydrolysis of nucleoside and deoxynucleoside triphosphates (NTP) by nucleophilic substitution at the rarely attacked ,!?-phosphorus, yielding pyrophosphate and a nucleotide (NMP) as products (Bhatnagar et al., 1991;Weber et al., 1992). Like other enzymes which catalyze substitution at the electron-rich ,!?-phosphorus, this enzyme requires two divalent cations for activity (Frick et al., 1994). The biological role of this enzyme is to prevent ' This work was supported in part by National Institutes of Health Grants DK28616 (to A.S.M.), GM18649 (to M.J.B.), and GM36358 (which supports A.G.G.).A complete listing of the distance restraints derived from the NOE data has been deposited at the Brookhaven Protein Data Bank (Chemistry Department, Brookhaven National Laboratory, Upton, NJ) together with the atomic coordinates of the family of 15 acceptable structures (file name IMUT).

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Section: Discussionmentioning

confidence: 99%

Solution Structure of the MutT Enzyme, a Nucleoside Triphosphate Pyrophosphohydrolase

Abeygunawardana¹,

Weber²,

Gittis³

et al. 1995

Biochemistry

124

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“…The main-chain conformations of the bulged residues are very irregular. For example, in mannose-binding protein (1MSB; Weis, 1991), the 4, II/ angles for position 1 are -120" and lo", respectively, and residue 2 is in the aL conformation. In another example, influenza virus neuraminidase (INSB; Burmeister, 1992), the 4, $ angles for position 1 are -90" and 13", respectively, and position 2 is again aL.…”

Section: Special Bulgesmentioning

confidence: 99%

Identification, classification, and analysis of beta‐bulges in proteins

et al. 1993

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A @-bulge is a region of irregularity in a &sheet involving two @-strands. It usually involves two or more residues in the bulged strand opposite to a single residue on the adjacent strand. These irregularities in 0-sheets were iden- A set of 182 protein chains (170 proteins) was used, and a total of 362 bulges were extracted. Five types of @-bulges were found: classic, G1, wide, bent, and special. Their characteristic amino acid preferences were found for most classes of bulges.Basically, bulges occur frequently in proteins; on average there are more than two bulges per protein. In general, @-bulges produce two main changes in the structure of a @-sheet: (1) disrupt the normal alternation of side-chain direction; (2) accentuate the twist of the sheet, altering the direction of the surrounding strands.

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“…The G3 CRD of human aggrecan was modelled by the rigid body fragment assembly method in HOMOLOGY (Biosym\MSI) by using the crystal structure of mannose-binding protein [15]. The Brookhaven database code is 2msb ; those for other structures are denoted by four-letter codes in parentheses.…”

Section: Protein Molecular Modellingmentioning

confidence: 99%

“…Crystal structures are known for mannose-binding protein, Eselectin and lithostathine in the CRD superfamily [15][16][17][18][19][20][21]. To correlate these with the G3 CRD structure, an alignment of 131 CRD sequences is reported in both Figures 2 and 3.…”

Section: Sequence Alignment and Residue Conservation In The Crd Supermentioning

confidence: 99%

“…Crystal structures are known for mannose-binding protein A and C, E-selectin, lithostathine and tetranectin in groups III, IV and VII [15][16][17][18][19][20][21]. The CRD contains a characteristic motif of two α-helices between which are three antiparallel β-strands (β), this motif being attached to three further β-strands in an upper region with two Ca# + -binding sites [22,23].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Conserved basic residues in the C-type lectin and short complement repeat domains of the G3 region of proteoglycans

Brissett

Perkins

1998

Biochemical Journal

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Aggrecan is the major proteoglycan of the extracellular matrix in cartilage. It contains two N-terminal globular regions, G1 and G2, and one C-terminal globular region, G3. G3 is implicated in the intracellular processing of aggrecan and contains a C-type lectin carbohydrate recognition domain (CRD), frequent occurrences of a C-terminal short complement repeat (SCR) domain, and occasionally an N-terminal epidermal growth factor domain. The CRD and SCR domains in 13 G3 sequences were each subjected to structural analysis. Alignment of 131 sequences from all seven groups in the CRD superfamily defined a consensus length of 136 residues, in which 32% of residues were conserved. Although the G3 CRD sequences agreed with this consensus, they also contained five fully conserved basic residues that are atypical of the CRD superfamily. Homology modelling showed that four of these residues are located on a surface region on the CRD that is separate from the Ca2+-binding residues involved in carbohydrate interactions. One conserved basic residue is identical in position with that of a conserved basic residue that mediates hyaluronate binding in the structurally related proteoglycan tandem repeat (PTR) domain in G1 and in link protein. The alignment of 13 G3 SCR sequences with 101 sequences in the SCR superfamily showed good agreement with conserved residues in the SCR superfamily. There are also five conserved basic residues in the G3 SCR that are atypical of the SCR superfamily, and homology modelling showed that all five were located on one surface of the SCR. It is concluded that both the CRD and SCR domains in G3 possess basic residues that are atypical of their superfamilies and might be related to function, and that the G3 CRD domain shows an evolutionary relationship to the PTR domain in G1.

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Structure of the Calcium-Dependent Lectin Domain from a Rat Mannose-Binding Protein Determined by MAD Phasing

Cited by 548 publications

References 52 publications

Solution Structure of the MutT Enzyme, a Nucleoside Triphosphate Pyrophosphohydrolase

Solution Structure of the MutT Enzyme, a Nucleoside Triphosphate Pyrophosphohydrolase

Identification, classification, and analysis of beta‐bulges in proteins

Conserved basic residues in the C-type lectin and short complement repeat domains of the G3 region of proteoglycans

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