Prostate Specific Antigen: A review

Mk, Brawer

doi:10.3109/02841869109092342

Cited by 31 publications

(18 citation statements)

References 34 publications

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“…It has received acceptance as a useful forensic marker of rape (Grave et al, 1985). However, the widest clinical interest in PSA is centered in its remarkable value as a serum marker for carcinoma of the prostate (Wang et al, 1979;Stamey, 1989;Brawer, 1991;Gittes, 1991;Oesterling, 1991). PSA is produced uniquely by the prostate and is made by normal, hyperplastic, and malignant prostatic tissue.…”

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confidence: 99%

A structural model for the prostate disease marker, human prostate‐specific antigen

1994

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Prostate-specific antigen (PSA) provides an excellent serum marker for prostate cancer, the most frequent form of cancer in American males. PSA is a 237-residue protease based on sequence homology to kallikrein-like enzymes. To predict the 3-dimensional structure of PSA, homology modeling studies were performed based on sequence and structural alignments with tonin, pancreatic kallikrein, chymotrypsin, and trypsin. The structurally conserved regions of the 4 reference X-ray proteins provided the core structure of PSA, whereas the loop structures were modeled on the loops of tonin and kallikrein. The unique "kallikrein loop" insert, between Ser 95b and Pro 95k of kallikrein, was constructed using molecular mechanics, dynamics, and electrostatics calculations. In the resulting PSA structure, the catalytic triad, involving residues His 57, Asp 102, and Ser 195, and hydrophobic and electrostatic interactions typical of serine proteases were extremely well conserved. Similarly, the 5 disulfide bonds of kallikrein were also conserved in PSA. These results, together with the fact that no major steric clashes arose during the modeling process, provide strong evidence for the validity of the PSA model. Calculation of the electrostatic potential contours of kallikrein and PSA was carried out using the finite difference Poisson-Boltzmann method. The calculations revealed matching areas of negative potential near the catalytic triad, but differences in the positive potential surrounding the active site. The PSA glycosylation site, Asn 61, is fully accessible to the solvent and is enclosed in a positive region of the isopotential map. The bottom of the substrate specificity pocket, residue S1, is a serine (Ser 189) as in chymotrypsin, rather than aspartate (Asp 189) as in tonin, kallikrein, and trypsin. This fact, plus other features of the S1 binding-pocket region, suggest that PSA would prefer substrates with hydrophobic residues at the P1 position. The location of a potential zinc ion binding site involving the side chain of histidines 91, 101, and 233 is also suggested. This PSA model should facilitate the understanding and prediction of structural and functional properties of this important cancer marker.

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confidence: 99%

A structural model for the prostate disease marker, human prostate‐specific antigen

1994

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“…While PSA correlates with clinical stage the prognostic value within each stage is limited [6,59], It appears that PSA reflects total tumor burden in an ade quate way. However, the important role of PSA in advanced cancer is for the evaluation of response to ther apy [6,15]. After initiation of antiandrogen therapy patients usually have a dramatic decrease of PSA.…”

Section: Prognostic Factors In Metastasized Prostatic Cancermentioning

confidence: 99%

Prostatic Cancer - What to Do?

Faul¹

1992

Eur Urol

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“…Quantitation of serum PSA (S-PSA) by the radioimmunoassay (RIA) technique has been a major achievement for early diagnosis and for monitoring response to therapy (3)(4)(5). The level of S-PSA has been studied in relation to volume, grade, and stage of carcinomas of the prostate (6 -10).…”

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confidence: 99%

“…In histopathology, immunostaining of tissue PSA has been used to identify cells of prostate origin (4,17,18). By qualitative or semiquantitative studies of tissue PSA, decreased tissue PSA levels were found in high-grade tumors (19,20).…”

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confidence: 99%